Immunology letters最新文献_第10页

Dendritic Cells: key controllers of lymphoid tissue organization 树突状细胞：淋巴组织组织的关键控制者。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-11-13 DOI: 10.1016/j.imlet.2025.107111

Alessia Calabrò , Claudia De Pasquale , Fabiana Drommi , Elena Giusto , Silvia Tamburini , Grazia Vento , Sayuri Yamazaki , Stefania Campana , Guido Ferlazzo

Dendritic cells (DCs) are highly efficient antigen-presenting cells that play a central role in inducing and controlling immune responses. Beyond their role in antigen presentation and in orchestrating lymphocyte activities, DCs also contribute to the spatial and functional organization of lymphoid structures, including both secondary and tertiary lymphoid organs, acting at different levels during both lymphoid tissue neogenesis and their maintenance.

DCs can facilitate lymphoid tissue development by interacting with both lymphoid tissue inducer and organizer cells, initiating early aggregation and supporting lymphotoxin-mediated signaling pathways essential for lymphoid structure maturation. Additionally, DCs release chemokines attracting and anchoring immune cells in lymphoid tissues and regulate the formation and the overall size of high endothelial venule system, which mediate immune cell trafficking into lymphoid tissues.

The dynamic crosstalk between DCs and fibroblastic reticular cells (FRC), which facilitate immune cell interactions and compartmentalization, is essential for lymphoid tissue specialization and function, though the precise cellular and molecular mechanisms of DC/FRC crosstalk remain to be fully elucidated.

Finally, studies in mice and humans suggest that DC subsets are pivotal in T follicular helper cell differentiation, essential for humoral immunity in B cell follicles of lymphoid tissues, therefore emphasizing DCs’ critical role also in supporting B cell maturation and antibody responses in the germinal centers of lymphoid organs.

树突状细胞（dc）是一种高效的抗原呈递细胞，在诱导和控制免疫反应中起着重要作用。除了在抗原呈递和协调淋巴细胞活动中发挥作用外，树突状细胞还参与淋巴组织的空间和功能组织，包括二级和三级淋巴器官，在淋巴组织新生和维持过程中发挥不同水平的作用。树突状细胞可以通过与淋巴组织诱导剂和组织者细胞相互作用来促进淋巴组织的发育，启动早期聚集并支持淋巴素介导的淋巴组织结构成熟所必需的信号通路。此外，dc释放趋化因子吸引和锚定淋巴组织中的免疫细胞，调节高内皮小静脉系统的形成和整体大小，介导免疫细胞转运到淋巴组织。DC和成纤维网状细胞（FRC）之间的动态串扰促进了免疫细胞的相互作用和区隔化，对淋巴组织的特化和功能至关重要，尽管DC/FRC串扰的确切细胞和分子机制仍有待充分阐明。最后，对小鼠和人类的研究表明，DC亚群在T滤泡辅助细胞分化中起关键作用，对淋巴组织B细胞滤泡的体液免疫至关重要，因此强调DC在淋巴器官生发中心支持B细胞成熟和抗体反应中的关键作用。

{"title":"Dendritic Cells: key controllers of lymphoid tissue organization","authors":"Alessia Calabrò , Claudia De Pasquale , Fabiana Drommi , Elena Giusto , Silvia Tamburini , Grazia Vento , Sayuri Yamazaki , Stefania Campana , Guido Ferlazzo","doi":"10.1016/j.imlet.2025.107111","DOIUrl":"10.1016/j.imlet.2025.107111","url":null,"abstract":"<div><div>Dendritic cells (DCs) are highly efficient antigen-presenting cells that play a central role in inducing and controlling immune responses. Beyond their role in antigen presentation and in orchestrating lymphocyte activities, DCs also contribute to the spatial and functional organization of lymphoid structures, including both secondary and tertiary lymphoid organs, acting at different levels during both lymphoid tissue neogenesis and their maintenance.</div><div>DCs can facilitate lymphoid tissue development by interacting with both lymphoid tissue inducer and organizer cells, initiating early aggregation and supporting lymphotoxin-mediated signaling pathways essential for lymphoid structure maturation. Additionally, DCs release chemokines attracting and anchoring immune cells in lymphoid tissues and regulate the formation and the overall size of high endothelial venule system, which mediate immune cell trafficking into lymphoid tissues.</div><div>The dynamic crosstalk between DCs and fibroblastic reticular cells (FRC), which facilitate immune cell interactions and compartmentalization, is essential for lymphoid tissue specialization and function, though the precise cellular and molecular mechanisms of DC/FRC crosstalk remain to be fully elucidated.</div><div>Finally, studies in mice and humans suggest that DC subsets are pivotal in T follicular helper cell differentiation, essential for humoral immunity in B cell follicles of lymphoid tissues, therefore emphasizing DCs’ critical role also in supporting B cell maturation and antibody responses in the germinal centers of lymphoid organs.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"278 ","pages":"Article 107111"},"PeriodicalIF":2.8,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Addressing the immunological gaps in asthma treatment: A call for region-specific research in Africa 解决哮喘治疗中的免疫学差距：呼吁在非洲开展区域特异性研究。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-11-11 DOI: 10.1016/j.imlet.2025.107110

Zemichael Getu Alemayehu, Brook Lelisa Sime, Abenezer Shiferaw Keraga

引用次数: 0

Anti-Yo antibody associated axial movement disorders – a novel phenotype in ANNS 抗yo抗体相关轴向运动障碍- ANNS的一种新表型。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-11-07 DOI: 10.1016/j.imlet.2025.107109

Ajith Cherian , Divya K P , Amod R , Deepa K P

Background

Movement disorders, as an anti-neuronal antibody mediated neurological syndrome(ANNS), is usually associated with anti-CV2/CRMP5,Hu/ANNA1 and Contactin-associated protein-like 2 (CASPR2) antibodies. Anti-Yo antibody associated movement disorders are extremely rare.

Methods

We analysed the data of 47 patients with anti –Yo antibodies who presented over a period of 5 years (2019–2024) in a tertiary care institute. Those with movement disorder phenotype, without ataxia, were included. Other etiologies were excluded with relevant work up.

Results

We report two elderly males in their sixties who presented with a subacute onset isolated progressive axial movement disorders, with positive anti-Yo antibody. One patient with axial myoclonus and camptocormia who did not initially respond to intravenous methylprednisolone had remarkable improvement with intravenous immunoglobulin and rituximab, while in the other treatment response was suboptimal.

Conclusion

Movement disorders due to anti-neuronal antibodies should be suspected when they develop subacutely, in older patients (> 50 years), have a progressive course beyond 3 months, associated with pain and constitutional symptoms like weight loss, all of which were present in our cases. Such intracellular Yo antigen induced ANNS usually have guarded response to immunomodulatory therapy compared to those mediated by antibodies against surface antigens, though one patient of ours had a remarkable improvement.

背景：运动障碍作为一种抗神经元抗体介导的神经综合征（ANNS），通常与抗cv2 /CRMP5、Hu/ANNA1和接触蛋白相关蛋白样2 （CASPR2）抗体相关。抗- yo抗体相关的运动障碍极为罕见。方法：我们分析了一家三级医疗机构5年（2019-2024）期间47例抗yo抗体患者的数据。包括运动障碍表型，无共济失调的患者。其他病因经相关工作排除。结果：我们报告了两名60多岁的老年男性，他们表现为亚急性发作的孤立进行性轴向运动障碍，抗yo抗体阳性。一名轴型肌阵挛和喜树病患者最初对静脉注射甲基强的松龙没有反应，但在静脉注射免疫球蛋白和利妥昔单抗后，情况有了显著改善，而在另一种治疗中，反应则不理想。结论：抗神经元抗体引起的运动障碍在发生亚急性时应予以怀疑，在老年患者（50岁以上）中，病程进展超过3个月，伴有疼痛和体重减轻等体质症状，所有这些都出现在我们的病例中。这种细胞内Yo抗原诱导的ANNS与表面抗原抗体介导的ANNS相比，通常对免疫调节治疗有保护反应，尽管我们的一位患者有显着改善。

{"title":"Anti-Yo antibody associated axial movement disorders – a novel phenotype in ANNS","authors":"Ajith Cherian , Divya K P , Amod R , Deepa K P","doi":"10.1016/j.imlet.2025.107109","DOIUrl":"10.1016/j.imlet.2025.107109","url":null,"abstract":"<div><h3>Background</h3><div>Movement disorders, as an anti-neuronal antibody mediated neurological syndrome(ANNS), is usually associated with anti-CV2/CRMP5,Hu/ANNA1 and Contactin-associated protein-like 2 (CASPR2) antibodies. Anti-Yo antibody associated movement disorders are extremely rare.</div></div><div><h3>Methods</h3><div>We analysed the data of 47 patients with anti –Yo antibodies who presented over a period of 5 years (2019–2024) in a tertiary care institute. Those with movement disorder phenotype, without ataxia, were included. Other etiologies were excluded with relevant work up.</div></div><div><h3>Results</h3><div>We report two elderly males in their sixties who presented with a subacute onset isolated progressive axial movement disorders, with positive anti-Yo antibody. One patient with axial myoclonus and camptocormia who did not initially respond to intravenous methylprednisolone had remarkable improvement with intravenous immunoglobulin and rituximab, while in the other treatment response was suboptimal.</div></div><div><h3>Conclusion</h3><div>Movement disorders due to anti-neuronal antibodies should be suspected when they develop subacutely, in older patients (> 50 years), have a progressive course beyond 3 months, associated with pain and constitutional symptoms like weight loss, all of which were present in our cases. Such intracellular Yo antigen induced ANNS usually have guarded response to immunomodulatory therapy compared to those mediated by antibodies against surface antigens, though one patient of ours had a remarkable improvement.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107109"},"PeriodicalIF":2.8,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145481997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Siglec-1+ macrophages in anti-tumor immunity siglec1 +巨噬细胞在抗肿瘤免疫中的作用

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-11-06 DOI: 10.1016/j.imlet.2025.107108

François-Xavier Mauvais , Peter van Endert

Macrophages expressing the sialic acid-binding lectin Siglec-1 are positioned strategically for uptake and filtering of antigenic material circulating through the lymphatic system into the subcapsular sinus of lymph nodes and through the blood into the marginal zone of the spleen. Siglec-1⁺ macrophages are also found in many tissues, frequently displaying an inflammatory profile. In secondary lymphoid organs, these cells are strategically positioned and play a role in adaptive immune responses by B, NK and T lymphocytes. A potential role of the cells in antitumor immunity has attracted significant scientific interest. This concept is supported by a report of dendritic cell-independent priming of a protective antitumor response by lymph node Siglec-1+ macrophages. Indeed, examination of preclinical models and human tumors has provided evidence for a dominant protective effect of lymph node Siglec-1+ macrophages in major types of solid tumors e.g. breast or colorectal cancer. In contrast, Siglec-1+ macrophages within tumor tissue have been found to be associated variably with favorable or unfavorable outcome depending on the model and tumor studied. We have recently demonstrated in mouse models that splenic Siglec-1+ macrophages in themarginal zone can prime protective tumor immunity against both tumors disseminating through the blood and tumors invading the spleen in the absence of type 1 conventional dendritic cells. Considering this, we postulate Siglec-1+ macrophages in all secondary lymphoid organs can prime potent antitumor responses. We propose that this capacity could be exploited for therapeutic stimulation of tumor immunity.

巨噬细胞表达唾液酸结合凝集素siglec1，通过淋巴系统进入淋巴结的包膜下窦，并通过血液进入脾脏边缘区，从而有策略地摄取和过滤抗原物质。siglec1 +巨噬细胞也存在于许多组织中，经常表现出炎症特征。在次级淋巴器官中，这些细胞被战略性地定位并在B、NK和T淋巴细胞的适应性免疫应答中发挥作用。这些细胞在抗肿瘤免疫中的潜在作用已经引起了科学界的极大兴趣。这一概念得到了淋巴结siglec1 +巨噬细胞不依赖树突状细胞启动保护性抗肿瘤反应的报道的支持。事实上，临床前模型和人类肿瘤的研究已经提供了证据，证明淋巴结siglec1 +巨噬细胞在主要类型的实体肿瘤（如乳腺癌或结直肠癌）中具有主要的保护作用。相反，肿瘤组织内的siglec1 +巨噬细胞根据所研究的模型和肿瘤，与有利或不利的结果有不同的相关性。我们最近在小鼠模型中证明，在没有1型常规树突状细胞的情况下，脾脏边缘区siglec1 +巨噬细胞可以对肿瘤通过血液传播和肿瘤侵入脾脏产生保护性肿瘤免疫。考虑到这一点，我们假设所有次级淋巴器官中的siglec1 +巨噬细胞都能引发有效的抗肿瘤反应。我们建议这种能力可以用于肿瘤免疫的治疗性刺激。

{"title":"Siglec-1+ macrophages in anti-tumor immunity","authors":"François-Xavier Mauvais , Peter van Endert","doi":"10.1016/j.imlet.2025.107108","DOIUrl":"10.1016/j.imlet.2025.107108","url":null,"abstract":"<div><div>Macrophages expressing the sialic acid-binding lectin Siglec-1 are positioned strategically for uptake and filtering of antigenic material circulating through the lymphatic system into the subcapsular sinus of lymph nodes and through the blood into the marginal zone of the spleen. Siglec-1<sup>+</sup> macrophages are also found in many tissues, frequently displaying an inflammatory profile. In secondary lymphoid organs, these cells are strategically positioned and play a role in adaptive immune responses by B, NK and T lymphocytes. A potential role of the cells in antitumor immunity has attracted significant scientific interest. This concept is supported by a report of dendritic cell-independent priming of a protective antitumor response by lymph node Siglec-1+ macrophages. Indeed, examination of preclinical models and human tumors has provided evidence for a dominant protective effect of lymph node Siglec-1+ macrophages in major types of solid tumors e.g. breast or colorectal cancer. In contrast, Siglec-1+ macrophages within tumor tissue have been found to be associated variably with favorable or unfavorable outcome depending on the model and tumor studied. We have recently demonstrated in mouse models that splenic Siglec-1+ macrophages in themarginal zone can prime protective tumor immunity against both tumors disseminating through the blood and tumors invading the spleen in the absence of type 1 conventional dendritic cells. Considering this, we postulate Siglec-1+ macrophages in all secondary lymphoid organs can prime potent antitumor responses. We propose that this capacity could be exploited for therapeutic stimulation of tumor immunity.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107108"},"PeriodicalIF":2.8,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PLIN2 exacerbates Allergic Rhinitis by inhibiting PINK1/Parkin-mediated mitophagy PLIN2通过抑制PINK1/ parkin介导的线粒体自噬而加重变应性鼻炎。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-11-03 DOI: 10.1016/j.imlet.2025.107107

Wangbo Yu , Shuai Zhang , Lijuan Peng , Jingwei Du

Objective

To investigate the pro-inflammatory role and underlying mechanism of Perilipin 2 (PLIN2) in Allergic Rhinitis (AR), focusing on its regulation of PINK1/Parkin-mediated mitophagy and the subsequent impact on lipid metabolism and oxidative stress.

Methods

Single-cell RNA sequencing (scRNA-seq) analysis was performed using GSE261706 from the GEO database, involving nasal mucosa from AR patients and healthy controls. A murine AR model was induced by ovalbumin (OVA), and human nasal epithelial cells (HNEpCs) were stimulated with Der p1. Interventions included AAV-mediated PLIN2 knockdown in vivo and siRNA-mediated knockdown in vitro. Techniques included Western blotting, qRT-PCR, flow cytometry, ELISA, and immunofluorescence/histological staining to assess PLIN2 expression, mitophagy, lipid accumulation, oxidative stress, and inflammatory responses.

Results

scRNA-seq analysis identified PLIN2 as a significantly upregulated gene in AR epithelial cells, which correlated with dysfunctional autophagy pathways. In both OVA-induced mice and Der p1-treated HNEpCs, PLIN2 expression was significantly elevated, accompanied by inhibited mitophagy (decreased LC3-II/I ratio, reduced PINK1/Parkin levels, and p62 accumulation), increased lipid deposition, and elevated ROS levels. PLIN2 knockdown markedly ameliorated AR pathology in mice, reducing inflammatory infiltration and serum levels of IgE, IL-4, and IL-5. Mechanistically, PLIN2 knockdown restored PINK1/Parkin-mediated mitophagy, decreased lipid accumulation, and attenuated ROS-induced cellular damage in HNEpCs.

Conclusions

PLIN2 exacerbates AR pathogenesis by inhibiting PINK1/Parkin-mediated mitophagy, promoting lipid accumulation and oxidative stress, and ultimately causing cellular damage in nasal epithelial cells. PLIN2 acts as a pivotal mediator linking metabolic dysregulation to inflammation, highlighting it as a promising therapeutic target for AR treatment.

目的：探讨Perilipin 2 （PLIN2）在变应性鼻炎（AR）中的促炎作用及其机制，重点研究其对PINK1/ parkin介导的线粒体自噬的调控及其对脂质代谢和氧化应激的影响。方法：使用GEO数据库中的GSE261706进行单细胞RNA测序（scRNA-seq）分析，研究对象为AR患者和健康对照组的鼻黏膜。用卵清蛋白（OVA）诱导小鼠AR模型，用Der p1刺激人鼻上皮细胞（HNEpCs）。干预包括体内aav介导的PLIN2敲低和体外sirna介导的PLIN2敲低。技术包括Western blotting、qRT-PCR、流式细胞术、ELISA和免疫荧光/组织学染色来评估PLIN2的表达、线粒体自噬、脂质积累、氧化应激和炎症反应。结果：scRNA-seq分析发现，PLIN2在AR上皮细胞中表达显著上调，与功能失调的自噬通路相关。在ova诱导小鼠和Der p1处理的HNEpCs中，PLIN2表达显著升高，同时线粒体自噬受到抑制（LC3-II/I比值降低，PINK1/Parkin水平降低，p62积累减少），脂质沉积增加，ROS水平升高。PLIN2敲低可显著改善小鼠AR病理，降低炎症浸润和血清IgE、IL-4和IL-5水平。在机制上，PLIN2敲低恢复了PINK1/ parkin介导的有丝分裂，减少了脂质积累，减轻了ros诱导的HNEpCs细胞损伤。结论：PLIN2通过抑制PINK1/ parkinson介导的线粒体自噬，促进脂质积累和氧化应激，最终导致鼻上皮细胞损伤，从而加剧AR的发病机制。PLIN2作为连接代谢失调和炎症的关键介质，突出表明它是AR治疗的一个有希望的治疗靶点。

{"title":"PLIN2 exacerbates Allergic Rhinitis by inhibiting PINK1/Parkin-mediated mitophagy","authors":"Wangbo Yu , Shuai Zhang , Lijuan Peng , Jingwei Du","doi":"10.1016/j.imlet.2025.107107","DOIUrl":"10.1016/j.imlet.2025.107107","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the pro-inflammatory role and underlying mechanism of Perilipin 2 (PLIN2) in Allergic Rhinitis (AR), focusing on its regulation of PINK1/Parkin-mediated mitophagy and the subsequent impact on lipid metabolism and oxidative stress.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing (scRNA-seq) analysis was performed using GSE261706 from the GEO database, involving nasal mucosa from AR patients and healthy controls. A murine AR model was induced by ovalbumin (OVA), and human nasal epithelial cells (HNEpCs) were stimulated with Der p1. Interventions included AAV-mediated PLIN2 knockdown in vivo and siRNA-mediated knockdown in vitro. Techniques included Western blotting, qRT-PCR, flow cytometry, ELISA, and immunofluorescence/histological staining to assess PLIN2 expression, mitophagy, lipid accumulation, oxidative stress, and inflammatory responses.</div></div><div><h3>Results</h3><div>scRNA-seq analysis identified PLIN2 as a significantly upregulated gene in AR epithelial cells, which correlated with dysfunctional autophagy pathways. In both OVA-induced mice and Der p1-treated HNEpCs, PLIN2 expression was significantly elevated, accompanied by inhibited mitophagy (decreased LC3-II/I ratio, reduced PINK1/Parkin levels, and p62 accumulation), increased lipid deposition, and elevated ROS levels. PLIN2 knockdown markedly ameliorated AR pathology in mice, reducing inflammatory infiltration and serum levels of IgE, IL-4, and IL-5. Mechanistically, PLIN2 knockdown restored PINK1/Parkin-mediated mitophagy, decreased lipid accumulation, and attenuated ROS-induced cellular damage in HNEpCs.</div></div><div><h3>Conclusions</h3><div>PLIN2 exacerbates AR pathogenesis by inhibiting PINK1/Parkin-mediated mitophagy, promoting lipid accumulation and oxidative stress, and ultimately causing cellular damage in nasal epithelial cells. PLIN2 acts as a pivotal mediator linking metabolic dysregulation to inflammation, highlighting it as a promising therapeutic target for AR treatment.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"278 ","pages":"Article 107107"},"PeriodicalIF":2.8,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human B-lymphopoiesis: Clinical challenges in B cell reconstitution and advances in in vitro modeling 人B淋巴系统：B细胞重建的临床挑战和体外模型的进展。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-11-03 DOI: 10.1016/j.imlet.2025.107106

Franziska Maria Schmidt , Marta Rizzi

The B cell compartment is maintained by continuous replenishment from hematopoietic stem cells (HSCs) and multipotent progenitors, as well as from B cell precursors. B cell depletion is a common therapeutic approach, not only in the context of B cell malignancies, but also in autoimmunity. The targeted elimination of B cells can be achieved through the use of chimeric antigen receptor (CAR)-T cells or monoclonal antibodies or bispecific antibodies that target both B and NK cells or B and T cells. When B cells are depleted, repopulation from bone marrow precursors occurs within three months to one year, following ontogeny. Nevertheless, prolonged B cell aplasia is observed in some patients and is associated with a progressive reduction of serum immunoglobulins and an increased susceptibility to infections. The mechanisms underlying such defects in B cell replenishment remain to be fully elucidated and studies on human B lymphopoiesis are needed in this context. Mouse models can be helpful in studying mechanisms of B cell development and the role of multiple (B cell-specific) genes in this process; however, they do not always mirror the human developmental dynamics and signals. Hence further tools are needed to study human B lymphopoiesis defects. In this review, we summarize the reported studies and cases of prolonged B cell aplasia following B cell depletion and discuss potential underlying causes. We then provide a comprehensive overview of the various in vitro models that can be used to study the dynamic of B lymphopoiesis to dissect B cell developmental defects in humans.

B细胞室由造血干细胞（hsc）和多能祖细胞以及B细胞前体的持续补充维持。B细胞消耗是一种常见的治疗方法，不仅在B细胞恶性肿瘤的背景下，而且在自身免疫。靶向消除B细胞可以通过使用嵌合抗原受体(CAR)-T细胞或针对B和NK细胞或B和T细胞的单克隆抗体或双特异性抗体来实现。当B细胞被耗尽时，在个体发生后的三个月到一年内，骨髓前体会发生再生。然而，在一些患者中观察到延长的B细胞发育不全，并与血清免疫球蛋白的进行性降低和对感染的易感性增加有关。这种B细胞补充缺陷的机制仍有待充分阐明，在这种背景下需要对人类B淋巴生成进行研究。小鼠模型有助于研究B细胞发育机制和多个（B细胞特异性）基因在这一过程中的作用；然而，它们并不总是反映人类发展的动态和信号。因此，需要进一步的工具来研究人类B淋巴系统缺陷。在这篇综述中，我们总结了B细胞耗竭后延长B细胞发育不全的研究报告和病例，并讨论了可能的潜在原因。然后，我们提供了各种体外模型的全面概述，这些模型可用于研究B淋巴生成的动态，以解剖人类B细胞发育缺陷。

{"title":"Human B-lymphopoiesis: Clinical challenges in B cell reconstitution and advances in in vitro modeling","authors":"Franziska Maria Schmidt , Marta Rizzi","doi":"10.1016/j.imlet.2025.107106","DOIUrl":"10.1016/j.imlet.2025.107106","url":null,"abstract":"<div><div>The B cell compartment is maintained by continuous replenishment from hematopoietic stem cells (HSCs) and multipotent progenitors, as well as from B cell precursors. B cell depletion is a common therapeutic approach, not only in the context of B cell malignancies, but also in autoimmunity. The targeted elimination of B cells can be achieved through the use of chimeric antigen receptor (CAR)-T cells or monoclonal antibodies or bispecific antibodies that target both B and NK cells or B and T cells. When B cells are depleted, repopulation from bone marrow precursors occurs within three months to one year, following ontogeny. Nevertheless, prolonged B cell aplasia is observed in some patients and is associated with a progressive reduction of serum immunoglobulins and an increased susceptibility to infections. The mechanisms underlying such defects in B cell replenishment remain to be fully elucidated and studies on human B lymphopoiesis are needed in this context. Mouse models can be helpful in studying mechanisms of B cell development and the role of multiple (B cell-specific) genes in this process; however, they do not always mirror the human developmental dynamics and signals. Hence further tools are needed to study human B lymphopoiesis defects. In this review, we summarize the reported studies and cases of prolonged B cell aplasia following B cell depletion and discuss potential underlying causes. We then provide a comprehensive overview of the various <em>in vitro</em> models that can be used to study the dynamic of B lymphopoiesis to dissect B cell developmental defects in humans.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107106"},"PeriodicalIF":2.8,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hydrogen therapy modulates nasal microbiota and metabolites in allergic rhinitis patients 氢疗法调节变应性鼻炎患者的鼻微生物群和代谢物

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-10-25 DOI: 10.1016/j.imlet.2025.107105

Nan Wang , Xingyue Zheng , Qianzi Ma , Yanlu Che , Wanchao Yang , Zhen Liu , Jingting Wang

<div><h3>Background</h3><div>Hydrogen is known to improve allergic rhinitis. Nasal microbiota that are different from those of healthy normal subjects have been detected in the nasal cavity of patients with allergic rhinitis (AR), and the microbiota can influence the metabolic levels of both themselves and their hosts. In addition, hydrogen has been shown to affect microbiota distribution and diversity. These findings suggest that hydrogen may target the nasal microbiota and metabolites to treat AR. Therefore, further in-depth exploration of the specific mechanism of action of hydrogen in the treatment of allergic rhinitis is necessary to provide a more scientific and effective program for the treatment of this disease. In this study, 35 patients with allergic rhinitis were selected as the experimental group, namely the HI group, and 35 healthy individuals were selected as the control group, namely the HC group.</div></div><div><h3>Methods</h3><div>The serum eosinophil count (EOS), immunoglobulin E (IgE) concentration, visual analogue scale (VAS) score, total nasal symptom score (TNSS), and rhinoconjunctivitis quality of life questionnaire (RQLQ) were used before and after hydrogen inhalation in AR patients. The skin prick test (SPT) was used to determine allergen sensitization. The community composition and relative abundance of the nasal microbiota were examined before and after hydrogen inhalation and in healthy subjects via 16S rRNA gene sequencing. Liquid chromatography‒mass spectrometry (LC‒MS) was used to explore the metabolic profile.</div></div><div><h3>Results</h3><div>There were no adverse reactions during or after hydrogen inhalation in AR patients, and the safety was good, with significant improvements in the VAS, TNSS, EOS, and IgE scores (<em>P</em> < 0.05). The results of 16S rRNA gene sequencing of nasal microbiota revealed that the distribution and diversity of nasal microbiota in AR patients were significantly altered after hydrogen inhalation compared with those before hydrogen inhalation and were closer to those of normal individuals. We also found that the metabolites 19(<em>R</em>)‑hydroxy-prostaglandin E2, arachidonic acid (AA), LEP 20:2, LEP O-18:2, LEP O-22:3, LPS 18:1, and LPS 20:3 were significantly more abundant than normal in nasal secretions in AR and then significantly decreased and approached normal levels after being modulated by hydrogen. 19(<em>R</em>)-Hydroxy-prostaglandin E2 levels were positively correlated with the abundance of Devosia, Paenibacillus, and colonies in the nasal cavity. AA was significantly positively correlated with Muribaculum bacteria and negatively correlated with [Eubacterium]_ruminantium_group. LPE was positively correlated with the bacteria Paenibacillus and Muribaculum and negatively correlated with [Eubacterium]_ruminantium_group. LPS was negatively correlated with [Eubacterium]_ruminantium_group and UCG-002 and positively correlated with Devosia and Muribaculum.</div></div><div><

众所周知，氢可以改善过敏性鼻炎。在变应性鼻炎（AR）患者的鼻腔中检测到与健康正常人不同的鼻腔微生物群，其微生物群可以影响自身和宿主的代谢水平。此外，氢气已被证明会影响微生物群的分布和多样性。这些发现提示，氢气可能针对鼻腔微生物群和代谢物治疗AR。因此，进一步深入探索氢气在变应性鼻炎治疗中的具体作用机制，为变应性鼻炎的治疗提供更科学有效的方案是必要的。本研究选取35例变应性鼻炎患者作为实验组，即HI组，选取35例健康个体作为对照组，即HC组。方法采用AR患者吸氢前后血清嗜酸性粒细胞计数（EOS）、免疫球蛋白E （IgE）浓度、视觉模拟评分（VAS）评分、鼻症状总评分（TNSS）和鼻结膜炎生活质量问卷（RQLQ）进行比较。采用皮肤点刺试验（SPT）测定过敏原致敏性。采用16S rRNA基因测序法检测吸氢前后及健康人鼻腔微生物群落组成及相对丰度。采用液相色谱-质谱（LC-MS）分析代谢谱。结果AR患者吸氢期间及吸氢后均无不良反应，安全性较好，VAS、TNSS、EOS、IgE评分均有显著改善（P < 0.05）。鼻腔微生物群16S rRNA基因测序结果显示，吸入氢气后，AR患者鼻腔微生物群的分布和多样性与吸入氢气前相比有明显改变，更接近正常人。我们还发现，AR鼻分泌物代谢产物19(R)‑羟基前列腺素E2、花生四烯酸（AA）、LEP 20:2、LEP O-18:2、LEP O-22:3、LPS 18:1和LPS 20:3的含量显著高于正常水平，经氢调节后显著降低并接近正常水平。19(R)-羟前列腺素E2水平与鼻内Devosia、Paenibacillus、菌落丰度呈正相关。AA与Muribaculum菌群呈显著正相关，与[Eubacterium]_ruminantium_group呈显著负相关。LPE与Paenibacillus和Muribaculum呈正相关，与[Eubacterium]_ruminantium_group负相关。LPS与[Eubacterium]_ruminantium_group和UCG-002呈负相关，与Devosia和Muribaculum呈正相关。结论氢干预可能通过调节AR患者鼻腔微生物群的种类组成和丰度分布，显著改变鼻腔微环境中关键代谢物的水平，重塑局部免疫微生态的失衡。这一机制的发现不仅揭示了氢对AR病理过程的潜在调控途径，同时也提示，作为一种无创、安全的干预手段，有望为临床实践提供一种新型的辅助治疗策略，有助于缓解患者鼻塞、流鼻涕、鼻痒等典型症状，提高患者的生活质量，为AR的个体化、精准化治疗开辟新思路。

{"title":"Hydrogen therapy modulates nasal microbiota and metabolites in allergic rhinitis patients","authors":"Nan Wang , Xingyue Zheng , Qianzi Ma , Yanlu Che , Wanchao Yang , Zhen Liu , Jingting Wang","doi":"10.1016/j.imlet.2025.107105","DOIUrl":"10.1016/j.imlet.2025.107105","url":null,"abstract":"<div><h3>Background</h3><div>Hydrogen is known to improve allergic rhinitis. Nasal microbiota that are different from those of healthy normal subjects have been detected in the nasal cavity of patients with allergic rhinitis (AR), and the microbiota can influence the metabolic levels of both themselves and their hosts. In addition, hydrogen has been shown to affect microbiota distribution and diversity. These findings suggest that hydrogen may target the nasal microbiota and metabolites to treat AR. Therefore, further in-depth exploration of the specific mechanism of action of hydrogen in the treatment of allergic rhinitis is necessary to provide a more scientific and effective program for the treatment of this disease. In this study, 35 patients with allergic rhinitis were selected as the experimental group, namely the HI group, and 35 healthy individuals were selected as the control group, namely the HC group.</div></div><div><h3>Methods</h3><div>The serum eosinophil count (EOS), immunoglobulin E (IgE) concentration, visual analogue scale (VAS) score, total nasal symptom score (TNSS), and rhinoconjunctivitis quality of life questionnaire (RQLQ) were used before and after hydrogen inhalation in AR patients. The skin prick test (SPT) was used to determine allergen sensitization. The community composition and relative abundance of the nasal microbiota were examined before and after hydrogen inhalation and in healthy subjects via 16S rRNA gene sequencing. Liquid chromatography‒mass spectrometry (LC‒MS) was used to explore the metabolic profile.</div></div><div><h3>Results</h3><div>There were no adverse reactions during or after hydrogen inhalation in AR patients, and the safety was good, with significant improvements in the VAS, TNSS, EOS, and IgE scores (<em>P</em> < 0.05). The results of 16S rRNA gene sequencing of nasal microbiota revealed that the distribution and diversity of nasal microbiota in AR patients were significantly altered after hydrogen inhalation compared with those before hydrogen inhalation and were closer to those of normal individuals. We also found that the metabolites 19(<em>R</em>)‑hydroxy-prostaglandin E2, arachidonic acid (AA), LEP 20:2, LEP O-18:2, LEP O-22:3, LPS 18:1, and LPS 20:3 were significantly more abundant than normal in nasal secretions in AR and then significantly decreased and approached normal levels after being modulated by hydrogen. 19(<em>R</em>)-Hydroxy-prostaglandin E2 levels were positively correlated with the abundance of Devosia, Paenibacillus, and colonies in the nasal cavity. AA was significantly positively correlated with Muribaculum bacteria and negatively correlated with [Eubacterium]_ruminantium_group. LPE was positively correlated with the bacteria Paenibacillus and Muribaculum and negatively correlated with [Eubacterium]_ruminantium_group. LPS was negatively correlated with [Eubacterium]_ruminantium_group and UCG-002 and positively correlated with Devosia and Muribaculum.</div></div><div><","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107105"},"PeriodicalIF":2.8,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High complement expression on extracellular vesicles in Covid-19 patients without pulmonary embolism leading to death. Case report 无肺栓塞死亡的Covid-19患者细胞外囊泡补体高表达病例报告。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-10-12 DOI: 10.1016/j.imlet.2025.107104

Apostolos Taxiarchis , Jovan Antovic , Olav Rooyackers , Gabriel Dumitrescu

This case report analyzes two severe COVID-19 patients without pulmonary embolism, revealing persistently elevated levels of extracellular vesicles (EVs) carrying tissue factor (TF+), complement proteins (C3a+, TCC+), and endothelial markers (CD144+, CD54+). Temporal trends in these EV subpopulations correlated with clinical deterioration, suggesting their role in endothelial injury, complement hyperactivation, and thromboinflammation. Notably, TF+EV dynamics aligned with anticoagulant treatment responses, while MPO+EVs reflected neutrophil activity without thrombotic complications. Despite differences in patient characteristics, these findings propose that patient-specific EV profiles may serve as potential indicators of disease progression, warranting targeted studies to validate their biomarker potential in severe COVID-19.

本病例报告分析了两例无肺栓塞的严重COVID-19患者，发现携带组织因子（TF+）、补体蛋白（C3a+、TCC+）和内皮标志物（CD144+、CD54+）的细胞外囊泡（ev）水平持续升高。这些EV亚群的时间趋势与临床恶化相关，表明它们在内皮损伤、补体过度激活和血栓炎症中的作用。值得注意的是，TF+EV动态与抗凝治疗反应一致，而MPO+EV反映中性粒细胞活性，无血栓并发症。尽管患者特征存在差异，但这些研究结果表明，患者特异性EV谱可能作为疾病进展的潜在指标，需要有针对性的研究来验证其在重症COVID-19中的生物标志物潜力。

引用次数: 0

Herpesvirus entry mediator on effector memory CD8+ T cells mediates the effects of sterol ester (27:1/18:1) levels on critical sepsis 效应记忆CD8+ T细胞的疱疹病毒进入介质介导甾醇酯（27:1/18:1）水平对严重败血症的影响

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-10-12 DOI: 10.1016/j.imlet.2025.107103

Junpu Cai , Haitao Li , Wenqiang Cui , Mingyu Hou , Huaiqian Bo , Ning Zhang , Yifan Wang , Jingwen Zhu , Caijun Tian

Background

Lipid metabolism is closely associated with the development of sepsis; however, the relationship between specific lipid molecules and sepsis remains unclear, as does the extent to which immune cell traits mediate the effects of lipid levels on critical sepsis.

Objective

The effects of lipids on critical sepsis were examined in this work, along with the potential mediating function of immune cell characteristics in this process, using Mendelian randomization.

Materials and Methods

A comprehensive two-sample Mendelian randomization analysis was conducted using genetic data from a genome-wide association study of 179 lipids, a large-scale genome-wide association study of 731 immune cell traits, and the latest genome-wide association study of critical sepsis. The ratios of immune cell trait indirect and mediating effects were computed using the coefficient product approach.

Results

We identified 4 lipids and 18 immune cell traits that had a negative causal relationship with critical sepsis, and 1 lipid and 13 immune cell traits that had a positive causal relationship with critical sepsis. Herpesvirus entry mediator (HVEM) on effector memory CD8+ T cells mediates the effects of sterol ester (27:1/18:1) levels on critical sepsis, accounting for 6.1% of this effect.

Conclusion

Our study confirmed the genetic causal relationship between lipids, immune cell traits, and critical sepsis, highlighting the potential mediating role of HVEM on effector memory CD8+ T cells and providing insights that may aid in the development of strategies for the prevention and treatment of critical sepsis in the clinic.

背景：脂质代谢与脓毒症的发生密切相关；然而，特异性脂质分子与脓毒症之间的关系尚不清楚，免疫细胞特性在多大程度上介导脂质水平对重症脓毒症的影响也不清楚。目的：本研究采用孟德尔随机化方法，探讨脂质对重症脓毒症的影响，以及免疫细胞特性在这一过程中的潜在介导作用。材料和方法：利用179种脂质全基因组关联研究、731种免疫细胞性状的大规模全基因组关联研究和最新的危重性脓毒症全基因组关联研究的遗传数据，进行全面的双样本孟德尔随机化分析。采用系数积法计算免疫细胞性状间接效应和中介效应的比值。结果：我们确定了4种脂质和18种免疫细胞特征与临界败血症具有负相关的因果关系，1种脂质和13种免疫细胞特征与临界败血症具有正相关的因果关系。效应记忆CD8+ T细胞上的疱疹病毒进入介质（HVEM）介导甾醇酯（27:1/18:1）水平对严重败血症的影响，占该效应的6.1%。结论：我们的研究证实了脂质、免疫细胞特性和重症脓毒症之间的遗传因果关系，突出了HVEM对效应记忆CD8+ T细胞的潜在介导作用，并为临床预防和治疗重症脓毒症的策略的制定提供了新的见解。

{"title":"Herpesvirus entry mediator on effector memory CD8+ T cells mediates the effects of sterol ester (27:1/18:1) levels on critical sepsis","authors":"Junpu Cai , Haitao Li , Wenqiang Cui , Mingyu Hou , Huaiqian Bo , Ning Zhang , Yifan Wang , Jingwen Zhu , Caijun Tian","doi":"10.1016/j.imlet.2025.107103","DOIUrl":"10.1016/j.imlet.2025.107103","url":null,"abstract":"<div><h3>Background</h3><div>Lipid metabolism is closely associated with the development of sepsis; however, the relationship between specific lipid molecules and sepsis remains unclear, as does the extent to which immune cell traits mediate the effects of lipid levels on critical sepsis.</div></div><div><h3>Objective</h3><div>The effects of lipids on critical sepsis were examined in this work, along with the potential mediating function of immune cell characteristics in this process, using Mendelian randomization.</div></div><div><h3>Materials and Methods</h3><div>A comprehensive two-sample Mendelian randomization analysis was conducted using genetic data from a genome-wide association study of 179 lipids, a large-scale genome-wide association study of 731 immune cell traits, and the latest genome-wide association study of critical sepsis. The ratios of immune cell trait indirect and mediating effects were computed using the coefficient product approach.</div></div><div><h3>Results</h3><div>We identified 4 lipids and 18 immune cell traits that had a negative causal relationship with critical sepsis, and 1 lipid and 13 immune cell traits that had a positive causal relationship with critical sepsis. Herpesvirus entry mediator (HVEM) on effector memory CD8+ T cells mediates the effects of sterol ester (27:1/18:1) levels on critical sepsis, accounting for 6.1% of this effect.</div></div><div><h3>Conclusion</h3><div>Our study confirmed the genetic causal relationship between lipids, immune cell traits, and critical sepsis, highlighting the potential mediating role of HVEM on effector memory CD8+ T cells and providing insights that may aid in the development of strategies for the prevention and treatment of critical sepsis in the clinic.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107103"},"PeriodicalIF":2.8,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Environmental determinants of immune tolerance in asthma and allergy 哮喘和过敏中免疫耐受的环境决定因素。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-10-10 DOI: 10.1016/j.imlet.2025.107102

Piia Karisola , Harri Alenius

Prevalence of allergic diseases has increased globally, reflecting environmental and behavioral changes. The exposome concept encompasses cumulative chemical, microbial, nutritional, psychosocial, and physical exposures across the life course, offering a unifying framework to understand how immune tolerance is shaped or disrupted. Emerging evidence highlights that early-life exposures are particularly critical. Pollutants, endocrine disruptors, microbial deprivation, dietary shifts, and psychosocial stress contribute to barrier dysfunction, dysbiosis, and immune dysregulation, favoring Th2 dominance and allergy development. In contrast, exposures that enhance biodiversity, microbial diversity, pollution-free air, and balanced nutrition support active tolerance development, especially via regulatory T cells. Mechanistic insights point to the barrier–microbiota–immune axis as central pathways linking the environment to allergic outcomes. Translational studies, including biodiversity enrichment interventions, maternal and infant dietary strategies, and microbiome-based therapies, illustrate the potential of exposome-informed approaches to allergy prevention. However, major challenges remain in measuring complex exposure mixtures, identifying causal pathways, and integrating exposome data with systems immunology. This review synthesizes current knowledge on how the exposome modulates immune tolerance and outlines future research directions toward precision prevention. A deeper understanding of these interactions is essential to address the rising global allergy burden.

过敏性疾病的患病率在全球范围内增加，反映了环境和行为的变化。暴露概念包括整个生命过程中累积的化学、微生物、营养、社会心理和物理暴露，提供了一个统一的框架来理解免疫耐受性是如何形成或破坏的。新出现的证据表明，生命早期的暴露尤为关键。污染物、内分泌干扰物、微生物剥夺、饮食变化和社会心理压力导致屏障功能障碍、生态失调和免疫失调，有利于Th2优势和过敏的发展。相比之下，增强生物多样性、微生物多样性、无污染空气和均衡营养的暴露支持主动耐受性的发展，特别是通过调节性T细胞。机制的见解指出屏障-微生物-免疫轴是连接环境和过敏结果的中心途径。转化研究，包括生物多样性富集干预、母婴饮食策略和基于微生物组的治疗，说明了暴露者知情方法预防过敏的潜力。然而，主要的挑战仍然是测量复杂的暴露混合物，确定因果途径，并将暴露数据与系统免疫学相结合。本文综述了目前有关暴露体如何调节免疫耐受的知识，并概述了未来精确预防的研究方向。更深入地了解这些相互作用对于解决日益增加的全球过敏负担至关重要。

{"title":"Environmental determinants of immune tolerance in asthma and allergy","authors":"Piia Karisola , Harri Alenius","doi":"10.1016/j.imlet.2025.107102","DOIUrl":"10.1016/j.imlet.2025.107102","url":null,"abstract":"<div><div>Prevalence of allergic diseases has increased globally, reflecting environmental and behavioral changes. The exposome concept encompasses cumulative chemical, microbial, nutritional, psychosocial, and physical exposures across the life course, offering a unifying framework to understand how immune tolerance is shaped or disrupted. Emerging evidence highlights that early-life exposures are particularly critical. Pollutants, endocrine disruptors, microbial deprivation, dietary shifts, and psychosocial stress contribute to barrier dysfunction, dysbiosis, and immune dysregulation, favoring Th2 dominance and allergy development. In contrast, exposures that enhance biodiversity, microbial diversity, pollution-free air, and balanced nutrition support active tolerance development, especially via regulatory T cells. Mechanistic insights point to the barrier–microbiota–immune axis as central pathways linking the environment to allergic outcomes. Translational studies, including biodiversity enrichment interventions, maternal and infant dietary strategies, and microbiome-based therapies, illustrate the potential of exposome-informed approaches to allergy prevention. However, major challenges remain in measuring complex exposure mixtures, identifying causal pathways, and integrating exposome data with systems immunology. This review synthesizes current knowledge on how the exposome modulates immune tolerance and outlines future research directions toward precision prevention. A deeper understanding of these interactions is essential to address the rising global allergy burden.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107102"},"PeriodicalIF":2.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0