Immunology letters最新文献_第5页

Establishing a system to identify correlations among immune system components for exploring alternative pathways for immune information transfer 建立一个系统来识别免疫系统成分之间的相关性，探索免疫信息传递的替代途径。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2026-02-01 Epub Date: 2025-09-09 DOI: 10.1016/j.imlet.2025.107085

Yaron Ilan

Introduction

The classic immune system information transfer occurs through direct cell-to-cell contact and the secretion of mediators. However, certain immune phenomena suggest alternative pathways exist between immune components that operate independently of these conventional mechanisms.

Methods

We used 24 male C57Bl/6 J mice, divided into six groups, to establish a system for testing alternative immune information transfer pathways. Two triggers—splenectomy and 24-hour fasting—were applied in various combinations. Splenocytes were prepared from operated mice and placed in sterile tubes within cages of different treatment groups. Ex vivo lymphocyte responses were measured using fluorescence-activated cell sorting (FACS) for cell epitope expression (CD4, CD8, CD25, Foxp3) and enzyme-linked immunosorbent assay (ELISA) for cytokine secretion (IFN-γ, TNF-α, IL-10, TGF-β).

Results

Significant changes were observed in CD25 and CD8+CD25 expression, as well as in IL-10 secretion, following the application of the triggers. The system exhibited inherent variability with trends toward altered immune responses in isolated splenocytes that had no direct contact with the trigger-exposed animals. Non-parametric analysis indicates a trend for these markers, even though there is significant variability within the groups..

Conclusions

The data suggest a system where correlations between immune components may occur through alternative pathways, indicating the possibility of non-conventional information transfer mechanisms in the immune system that require further investigation.

经典的免疫系统信息传递是通过细胞间的直接接触和介质的分泌来实现的。然而，某些免疫现象表明，在独立于这些常规机制的免疫成分之间存在替代途径。方法：选取24只雄性C57Bl/6J小鼠，分为6组，建立免疫信息传递替代途径检测系统。脾切除术和24小时禁食两种触发法以不同的组合应用。取手术后小鼠脾细胞，置于不同处理组笼内无菌管中。体外淋巴细胞反应采用荧光活化细胞分选（FACS）检测细胞表位表达（CD4、CD8、CD25、Foxp3），酶联免疫吸附法（ELISA）检测细胞因子分泌（IFN-γ、TNF-α、IL-10、TGF-β）。结果：应用触发剂后，CD25和CD8+CD25的表达以及IL-10的分泌发生了显著变化。该系统表现出固有的可变性，在与暴露于触发器的动物没有直接接触的分离脾细胞中，有改变免疫反应的趋势。非参数分析表明了这些标记物的趋势，尽管在组内存在显著的差异。结论：数据表明免疫成分之间的相关性可能通过其他途径发生，表明免疫系统中非传统信息传递机制的可能性需要进一步研究。

{"title":"Establishing a system to identify correlations among immune system components for exploring alternative pathways for immune information transfer","authors":"Yaron Ilan","doi":"10.1016/j.imlet.2025.107085","DOIUrl":"10.1016/j.imlet.2025.107085","url":null,"abstract":"<div><h3>Introduction</h3><div>The classic immune system information transfer occurs through direct cell-to-cell contact and the secretion of mediators. However, certain immune phenomena suggest alternative pathways exist between immune components that operate independently of these conventional mechanisms.</div></div><div><h3>Methods</h3><div>We used 24 male C57Bl/6 J mice, divided into six groups, to establish a system for testing alternative immune information transfer pathways. Two triggers—splenectomy and 24-hour fasting—were applied in various combinations. Splenocytes were prepared from operated mice and placed in sterile tubes within cages of different treatment groups. Ex vivo lymphocyte responses were measured using fluorescence-activated cell sorting (FACS) for cell epitope expression (CD4, CD8, CD25, Foxp3) and enzyme-linked immunosorbent assay (ELISA) for cytokine secretion (IFN-γ, TNF-α, IL-10, TGF-β).</div></div><div><h3>Results</h3><div>Significant changes were observed in CD25 and CD8+CD25 expression, as well as in IL-10 secretion, following the application of the triggers. The system exhibited inherent variability with trends toward altered immune responses in isolated splenocytes that had no direct contact with the trigger-exposed animals. Non-parametric analysis indicates a trend for these markers, even though there is significant variability within the groups..</div></div><div><h3>Conclusions</h3><div>The data suggest a system where correlations between immune components may occur through alternative pathways, indicating the possibility of non-conventional information transfer mechanisms in the immune system that require further investigation.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107085"},"PeriodicalIF":2.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039666","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

Immune checkpoint molecules as predictive markers of COVID-19 severity: A comprehensive univariable and multivariable analysis 免疫检查点分子作为COVID-19严重程度的预测标志物：一项综合单变量和多变量分析

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2026-02-01 Epub Date: 2025-09-15 DOI: 10.1016/j.imlet.2025.107089

Adam Majchrzak , Paulina Niedźwiedzka-Rystwej , Dominika Bębnowska , Bogusz Aksak-Wąs , Malwina Karasińska-Cieślak , Danuta Cembrowska-Lech , Karolina Skonieczna-Żydecka , Kaja Mielczak , Anna Urbańska , Rafał Hrynkiewicz , Filip Lewandowski , Miłosz Parczewski

Immune dysregulation plays a key role in the deterioration of COVID-19. This study evaluated immune checkpoint molecules (ICMs) as markers of disease severity. Immunophenotyping of 525 hospitalised patients with moderate (n=464) and severe (n=61) COVID-19 was performed at admission and analysed alongside clinical, laboratory, and imaging data. The strongest correlations with severe outcomes and mortality were found for CD200R+CD3+ T and CD19+ B cells. Significant differences in PD-1+ and PD-L1+ lymphocyte subsets were observed between severity groups. Machine learning (SHAP) confirmed that ICM expression was at least as predictive as conventional risk factors. These findings suggest that markers of immune exhaustion, especially PD-1, PD-L1, and CD200R, may help predict COVID-19 severity. Further research is needed to determine whether targeting immune checkpoints could improve outcomes.

免疫失调是COVID-19恶化的关键因素。这项研究评估了免疫检查点分子（ICMs）作为疾病严重程度的标志物。在入院时对525名中度（n=464）和重度（n=61） COVID-19住院患者进行免疫分型，并结合临床、实验室和影像学数据进行分析。CD200R+CD3+ T和CD19+ B细胞与严重结局和死亡率的相关性最强。严重程度组间PD-1+和PD-L1+淋巴细胞亚群差异有统计学意义。机器学习（SHAP）证实，ICM表达至少与传统风险因素一样具有预测性。这些发现表明，免疫衰竭标志物，特别是PD-1、PD-L1和CD200R，可能有助于预测COVID-19的严重程度。需要进一步的研究来确定靶向免疫检查点是否可以改善结果。

{"title":"Immune checkpoint molecules as predictive markers of COVID-19 severity: A comprehensive univariable and multivariable analysis","authors":"Adam Majchrzak , Paulina Niedźwiedzka-Rystwej , Dominika Bębnowska , Bogusz Aksak-Wąs , Malwina Karasińska-Cieślak , Danuta Cembrowska-Lech , Karolina Skonieczna-Żydecka , Kaja Mielczak , Anna Urbańska , Rafał Hrynkiewicz , Filip Lewandowski , Miłosz Parczewski","doi":"10.1016/j.imlet.2025.107089","DOIUrl":"10.1016/j.imlet.2025.107089","url":null,"abstract":"<div><div>Immune dysregulation plays a key role in the deterioration of COVID-19. This study evaluated immune checkpoint molecules (ICMs) as markers of disease severity. Immunophenotyping of 525 hospitalised patients with moderate (n=464) and severe (n=61) COVID-19 was performed at admission and analysed alongside clinical, laboratory, and imaging data. The strongest correlations with severe outcomes and mortality were found for CD200R+CD3+ T and CD19+ B cells. Significant differences in PD-1+ and PD-L1+ lymphocyte subsets were observed between severity groups. Machine learning (SHAP) confirmed that ICM expression was at least as predictive as conventional risk factors. These findings suggest that markers of immune exhaustion, especially PD-1, PD-L1, and CD200R, may help predict COVID-19 severity. Further research is needed to determine whether targeting immune checkpoints could improve outcomes.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107089"},"PeriodicalIF":2.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080515","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

ELF3 promotes the development of psoriasis through transcriptional up-regulation of ADAM8 expression ELF3通过上调ADAM8的转录表达促进银屑病的发展。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2026-02-01 Epub Date: 2025-08-08 DOI: 10.1016/j.imlet.2025.107069

Yu Zhang , Nannan Tong , Siyu Hao , He Ma , Yuzhen Li

Psoriasis is a systemic inflammatory disorder that has a significant impact on the quality of life of patients. E74-like factor 3 (ELF3) is a common transcriptional mediator of inflammation, but the effect of ELF3 on psoriasis development and severity is poorly understood. In this study, we first collected clinical normal skin tissues and skin tissues of psoriasis patients to detect the mRNA and protein levels of ELF3 and found that ELF3 was highly expressed in psoriasis skin tissues. We further used the imiquimod (IMQ)-induced mice model to mimic the phenotypic changes of human psoriasis in vivo, which are manifested as scaling, epidermal hyperplasia, and erythema formation, but knockdown of ELF3 resulted in suppression of these phenomena. In addition, downregulation of ELF3 expression inhibited neoangiogenesis and inflammatory cell infiltration. On this basis, we further found that ELF3 promotes the proliferation, angiogenesis, and inflammatory response of human keratinocyte HaCaT in vitro. Mechanistically, we found that ELF3 transcriptionally activated the activity of the downstream factor ADAM metallopeptidase domain 8 (ADAM8) by dual luciferase assays, thereby exacerbating the severity of psoriasis. We concluded that ELF3 is a key target for exacerbating psoriasis pathologic manifestations and promoting disease progression.

牛皮癣是一种系统性炎症性疾病，对患者的生活质量有显著影响。e74样因子3 （ELF3）是一种常见的炎症转录介质，但ELF3对银屑病发展和严重程度的影响尚不清楚。在本研究中，我们首先采集临床正常皮肤组织和银屑病患者皮肤组织，检测ELF3 mRNA和蛋白水平，发现ELF3在银屑病皮肤组织中高表达。我们进一步利用咪喹莫特（IMQ）诱导的小鼠模型，模拟人银屑病在体内的表型变化，表现为脱屑、表皮增生和红斑形成，但敲低ELF3可抑制这些现象。此外，下调ELF3表达可抑制新生血管生成和炎症细胞浸润。在此基础上，我们进一步发现ELF3在体外促进人角化细胞HaCaT的增殖、血管生成和炎症反应。在机制上，我们通过双荧光素酶检测发现ELF3转录激活下游因子ADAM金属肽酶结构域8 （ADAM8）的活性，从而加重银屑病的严重程度。我们得出结论，ELF3是加重银屑病病理表现和促进疾病进展的关键靶点。

{"title":"ELF3 promotes the development of psoriasis through transcriptional up-regulation of ADAM8 expression","authors":"Yu Zhang , Nannan Tong , Siyu Hao , He Ma , Yuzhen Li","doi":"10.1016/j.imlet.2025.107069","DOIUrl":"10.1016/j.imlet.2025.107069","url":null,"abstract":"<div><div>Psoriasis is a systemic inflammatory disorder that has a significant impact on the quality of life of patients. E74-like factor 3 (ELF3) is a common transcriptional mediator of inflammation, but the effect of ELF3 on psoriasis development and severity is poorly understood. In this study, we first collected clinical normal skin tissues and skin tissues of psoriasis patients to detect the mRNA and protein levels of ELF3 and found that ELF3 was highly expressed in psoriasis skin tissues. We further used the imiquimod (IMQ)-induced mice model to mimic the phenotypic changes of human psoriasis <em>in vivo</em>, which are manifested as scaling, epidermal hyperplasia, and erythema formation, but knockdown of ELF3 resulted in suppression of these phenomena. In addition, downregulation of ELF3 expression inhibited neoangiogenesis and inflammatory cell infiltration. On this basis, we further found that ELF3 promotes the proliferation, angiogenesis, and inflammatory response of human keratinocyte HaCaT <em>in vitro</em>. Mechanistically, we found that ELF3 transcriptionally activated the activity of the downstream factor ADAM metallopeptidase domain 8 (ADAM8) by dual luciferase assays, thereby exacerbating the severity of psoriasis. We concluded that ELF3 is a key target for exacerbating psoriasis pathologic manifestations and promoting disease progression.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107069"},"PeriodicalIF":2.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816545","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

The essential integration of sex and gender in immunological research 性别与社会性别在免疫学研究中的重要整合。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2026-02-01 Epub Date: 2025-10-09 DOI: 10.1016/j.imlet.2025.107097

Marcus Altfeld , Camila Consiglio , Darragh Duffy , Molly Ingersoll , Cliona O'Farrelly , Tal Pecht , Tal Shay , Helena Soares

引用次数: 0

Tissue resident memory B cells mediate protective immunity to respiratory pathogens in the airways 组织常驻记忆B细胞介导呼吸道病原体的保护性免疫。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2026-02-01 Epub Date: 2025-09-16 DOI: 10.1016/j.imlet.2025.107091

Ivy M. Akehurst, Louisa K. James

Respiratory pathogens pose a significant risk to public health and are responsible for burdening health care by causing worldwide morbidity and mortality. The immune environment in the airway is critical for protection from respiratory pathogens and comprises several specialist subsets of resident lymphocytes and myeloid cells. Tissue resident-memory B cells (B_RM) are a subset of memory B cell which reside in mucosal tissues, including the airways. Although, B_RM have only recently been characterised, they have a crucial role in generating robust and localised immune responses to respiratory infections, particularly secondary responses, by rapidly differentiating into antibody-secreting cells. A greater understanding of their role in protecting the airways from respiratory pathogens will enable the development of immunisation strategies against respiratory disease. This mini-review aims to summarise the current knowledge of B_RM and highlight areas for future research.

呼吸道病原体对公共卫生构成重大风险，并通过在世界范围内造成发病率和死亡率，给卫生保健造成负担。气道内的免疫环境对保护机体免受呼吸道病原体的侵袭至关重要，它由若干专门的淋巴细胞和骨髓细胞亚群组成。组织驻留记忆B细胞（Tissue resident-memory B cells， BRM）是记忆B细胞的一个子集，存在于包括气道在内的粘膜组织中。尽管BRM最近才被描述，但它们通过迅速分化为抗体分泌细胞，在产生针对呼吸道感染的强大和局部免疫反应，特别是继发性反应方面发挥着至关重要的作用。更好地了解它们在保护呼吸道免受呼吸道病原体侵害方面的作用，将有助于制定针对呼吸道疾病的免疫策略。这篇小型综述旨在总结BRM的当前知识，并强调未来研究的领域。

引用次数: 0

Immunological features driving distinct repigmentation patterns in patients with stable vitiligo submitted to the autologous keratinocyte/melanocyte transplantation 在接受自体角质细胞/黑素细胞移植的稳定型白癜风患者中，免疫特征驱动不同的再色素沉着模式。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2026-02-01 Epub Date: 2025-10-02 DOI: 10.1016/j.imlet.2025.107098

Bruna Estefânia Diniz Frias , Roberta Oliveira Prado , Mariana Gontijo Ramos , Nathália Werneck Cézar de Oliveira , Fernanda Fortes de Araújo , Liliane Martins dos Santos , Camila Gontijo Ramos , Camila Bechara Kallás , Maria Sílvia Laborne Alves de Sousa , Ismael Artur Costa-Rocha , Joaquim Pedro Brito-de-Sousa , Rachel Basques Caligiorne , Marcelo Antônio Pascoal-Xavier , Vanessa Peruhype-Magalhães , Daniel Gontijo Ramos , Andréa Teixeira-Carvalho , Olindo Assis Martins-Filho

This study aimed to characterize biomarkers of therapeutic response in patients with stable vitiligo undergoing the autologous non-cultured keratinocyte/melanocyte transplantation. The approaches performed were systemic analysis evaluated during pre-transplantation/(D0), seven/(D7), and 28 or more/(D28–45) days after the procedure and compartmentalized analysis in epidermal cell suspension (explant). Increased number of pro-inflammatory monocytes and NK-cells was found during the transplantation follow-up in vitiligo patients compared to the control. There were higher numbers of CD8⁺ T-cells and CD4⁺HLA-DR⁺ T-cells circulating at D28–45 compared to D0, and increased number of CD8⁺HLA-DR⁺ T-cells at D28–45 compared to D7. Decreased levels of the most pro-inflammatory chemokines/cytokines during post-transplantation kinetics timeline were observed. Integrative analysis demonstrated that patients with unsatisfactory repigmentation presented higher numbers of connections between the blood/skin components at D0. The data suggest differentiated profiles in the dynamics of the hematological/immunological biomarkers, according to the kinetics timeline and the clinical outcome of repigmentation in vitiligo patients.

本研究旨在描述稳定性白癜风患者接受自体非培养角质细胞/黑素细胞移植治疗反应的生物标志物。所采用的方法是在移植前/(D0)、7 /(D7)和28/(D28-45)天进行系统分析，并在表皮细胞悬液（外植体）中进行区隔分析。与对照组相比，白癜风患者在移植随访期间发现促炎单核细胞和nk细胞数量增加。与D0相比，D28-45时循环的CD8+ t细胞和CD4+HLA-DR+ t细胞数量增加，D28-45时循环的CD8+HLA-DR+ t细胞数量比D7增加。在移植后的动力学时间线中，观察到大多数促炎趋化因子/细胞因子水平下降。综合分析表明，重新着色不满意的患者在D0时血液/皮肤成分之间的连接数量更多。这些数据表明，根据白癜风患者的动力学时间线和临床结果，血液学/免疫学生物标志物的动力学存在差异。

{"title":"Immunological features driving distinct repigmentation patterns in patients with stable vitiligo submitted to the autologous keratinocyte/melanocyte transplantation","authors":"Bruna Estefânia Diniz Frias , Roberta Oliveira Prado , Mariana Gontijo Ramos , Nathália Werneck Cézar de Oliveira , Fernanda Fortes de Araújo , Liliane Martins dos Santos , Camila Gontijo Ramos , Camila Bechara Kallás , Maria Sílvia Laborne Alves de Sousa , Ismael Artur Costa-Rocha , Joaquim Pedro Brito-de-Sousa , Rachel Basques Caligiorne , Marcelo Antônio Pascoal-Xavier , Vanessa Peruhype-Magalhães , Daniel Gontijo Ramos , Andréa Teixeira-Carvalho , Olindo Assis Martins-Filho","doi":"10.1016/j.imlet.2025.107098","DOIUrl":"10.1016/j.imlet.2025.107098","url":null,"abstract":"<div><div>This study aimed to characterize biomarkers of therapeutic response in patients with stable vitiligo undergoing the autologous non-cultured keratinocyte/melanocyte transplantation. The approaches performed were systemic analysis evaluated during pre-transplantation/(D0), seven/(D7), and 28 or more/(D28–45) days after the procedure and compartmentalized analysis in epidermal cell suspension (explant). Increased number of pro-inflammatory monocytes and NK-cells was found during the transplantation follow-up in vitiligo patients compared to the control. There were higher numbers of CD8<sup>+</sup> <em>T</em>-cells and CD4<sup>+</sup>HLA-DR<sup>+</sup> <em>T</em>-cells circulating at D28–45 compared to D0, and increased number of CD8<sup>+</sup>HLA-DR<sup>+</sup> <em>T</em>-cells at D28–45 compared to D7. Decreased levels of the most pro-inflammatory chemokines/cytokines during post-transplantation kinetics timeline were observed. Integrative analysis demonstrated that patients with unsatisfactory repigmentation presented higher numbers of connections between the blood/skin components at D0. The data suggest differentiated profiles in the dynamics of the hematological/immunological biomarkers, according to the kinetics timeline and the clinical outcome of repigmentation in vitiligo patients.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107098"},"PeriodicalIF":2.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228437","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

Restoration of Fli1 expression as a potential therapeutic approach in Systemic Sclerosis: Effects on age-associated B cells 恢复Fli1表达作为系统性硬化症的潜在治疗方法：对年龄相关B细胞的影响

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2026-02-01 Epub Date: 2025-09-26 DOI: 10.1016/j.imlet.2025.107094

Athanasios Sachinidis , Malamatenia Lamprinou , Theodoros Dimitroulas

Fli1 is a transcription factor playing a major role in the regulation of normal hematopoiesis and vasculogenesis. Its deficiency has been associated with the development of fibrosis in various diseases, including systemic sclerosis/scleroderma (SSc), a rare autoimmune rheumatic disease. In addition, in Fli1 B cell conditional knockout mice, a striking increase of age-associated B cells (ABCs) has been observed. These cells constitute a CD11c⁺CD21^low/- B cell population that displays an expansion in autoimmunity and drives disease pathogenesis. The exact role and functions of ABCs, though, are not yet fully understood. Taking into consideration all the above, regarding Fli1 deficiency in SSc pathogenesis and ABC expansion, we propose restoration of this specific transcription factor’s expression as a potential therapeutic approach for the aforementioned rheumatic disease. Moreover, we provide some interventions that aim to restore Fli1 expression via modulating the signals of TGF-β pathway, whose activation is considered as crucial for fibrosis development in SSc.

Fli1是一种转录因子，在正常造血和血管发生的调节中起重要作用。它的缺乏与各种疾病纤维化的发展有关，包括系统性硬化症/硬皮病（SSc），一种罕见的自身免疫性风湿病。此外，在Fli1 B细胞条件敲除小鼠中，观察到年龄相关B细胞（abc）的显著增加。这些细胞构成CD11c+CD21low/- B细胞群，在自身免疫中表现出扩张并驱动疾病发病机制。然而，abc的确切作用和功能尚不完全清楚。综上所述，关于SSc发病机制中的Fli1缺陷和ABC扩增，我们建议恢复这一特定转录因子的表达作为上述风湿性疾病的潜在治疗方法。此外，我们提供了一些干预措施，旨在通过调节TGF-β通路的信号来恢复Fli1的表达，TGF-β通路的激活被认为是SSc纤维化发展的关键。

{"title":"Restoration of Fli1 expression as a potential therapeutic approach in Systemic Sclerosis: Effects on age-associated B cells","authors":"Athanasios Sachinidis , Malamatenia Lamprinou , Theodoros Dimitroulas","doi":"10.1016/j.imlet.2025.107094","DOIUrl":"10.1016/j.imlet.2025.107094","url":null,"abstract":"<div><div>Fli1 is a transcription factor playing a major role in the regulation of normal hematopoiesis and vasculogenesis. Its deficiency has been associated with the development of fibrosis in various diseases, including systemic sclerosis/scleroderma (SSc), a rare autoimmune rheumatic disease. In addition, in <em>Fli1</em> B cell conditional knockout mice, a striking increase of age-associated B cells (ABCs) has been observed. These cells constitute a CD11c<sup>+</sup>CD21<sup>low/-</sup> B cell population that displays an expansion in autoimmunity and drives disease pathogenesis. The exact role and functions of ABCs, though, are not yet fully understood. Taking into consideration all the above, regarding Fli1 deficiency in SSc pathogenesis and ABC expansion, we propose restoration of this specific transcription factor’s expression as a potential therapeutic approach for the aforementioned rheumatic disease. Moreover, we provide some interventions that aim to restore Fli1 expression via modulating the signals of TGF-β pathway, whose activation is considered as crucial for fibrosis development in SSc.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107094"},"PeriodicalIF":2.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185729","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 : 2026-02-01 Epub 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":"2026-02-01","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

Machine learning in allergy research: A bibliometric review 过敏研究中的机器学习：文献计量学综述。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2026-02-01 Epub Date: 2025-09-08 DOI: 10.1016/j.imlet.2025.107088

Ellen Kong , Alex Cucco , Adnan Custovic , Sara Fontanella

The emergence of big data and analytic approaches initiated research efforts to characterise different subtypes of allergic diseases, including tracking disease progression and identifying patterns that may offer insight into their development and progression. Triangulation from different data sources and study types may help to elucidate the directionality of relationships between variables at a very individual level by modelling the complex interdependencies between multiple dimensions (e.g., genome, transcriptome, epigenome, microbiome, and metabolome), thereby moving away from associative to a more causal analysis. To ascertain the role of machine learning in allergy research, we conducted a comprehensive systematic review of the current literature. The findings highlight and underscore the potential of using AI/ML approaches in advancing our understanding of allergic diseases, which ultimately enhances patient care through improved prevention, diagnosis, and management strategies. It is important to emphasise that there is no single ‘best’ analytical method, highlighting the importance of cross-disciplinary collaborations. A team science approach is crucial for ensuring the application of appropriate methodologies tailored to the research question at hand and that context-specific interpretations are being made, supported by critical appraisal from both the front- (e.g., clinicians) and back-end (e.g., analysts) of research processes.

大数据和分析方法的出现启动了研究工作，以表征不同亚型的过敏性疾病，包括跟踪疾病进展和识别可能提供深入了解其发展和进展的模式。通过对多个维度（如基因组、转录组、表观基因组、微生物组和代谢组）之间复杂的相互依赖性进行建模，来自不同数据源和研究类型的三角测量可能有助于在非常个体的水平上阐明变量之间关系的方向性，从而从关联分析转向因果分析。为了确定机器学习在过敏研究中的作用，我们对当前文献进行了全面系统的回顾。这些发现突出并强调了使用AI/ML方法在提高我们对过敏性疾病的理解方面的潜力，并最终通过改进预防、诊断和管理策略来增强患者护理。重要的是要强调没有单一的“最佳”分析方法，强调跨学科合作的重要性。团队科学方法对于确保应用适合手头研究问题的适当方法至关重要，并且在研究过程的前端（例如临床医生）和后端（例如分析人员）进行批判性评估的支持下，正在做出具体情况的解释。

{"title":"Machine learning in allergy research: A bibliometric review","authors":"Ellen Kong , Alex Cucco , Adnan Custovic , Sara Fontanella","doi":"10.1016/j.imlet.2025.107088","DOIUrl":"10.1016/j.imlet.2025.107088","url":null,"abstract":"<div><div>The emergence of big data and analytic approaches initiated research efforts to characterise different subtypes of allergic diseases, including tracking disease progression and identifying patterns that may offer insight into their development and progression. Triangulation from different data sources and study types may help to elucidate the directionality of relationships between variables at a very individual level by modelling the complex interdependencies between multiple dimensions (e.g., genome, transcriptome, epigenome, microbiome, and metabolome), thereby moving away from associative to a more causal analysis. To ascertain the role of machine learning in allergy research, we conducted a comprehensive systematic review of the current literature. The findings highlight and underscore the potential of using AI/ML approaches in advancing our understanding of allergic diseases, which ultimately enhances patient care through improved prevention, diagnosis, and management strategies. It is important to emphasise that there is no single ‘best’ analytical method, highlighting the importance of cross-disciplinary collaborations. A team science approach is crucial for ensuring the application of appropriate methodologies tailored to the research question at hand and that context-specific interpretations are being made, supported by critical appraisal from both the front- (e.g., clinicians) and back-end (e.g., analysts) of research processes.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107088"},"PeriodicalIF":2.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033098","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

Analysis of islet antigen-specific autoreactive T cells from Japanese patients with slowly progressive insulin-dependent diabetes mellitus 日本缓慢进展型胰岛素依赖型糖尿病患者胰岛抗原特异性自身反应性T细胞分析。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2026-02-01 Epub Date: 2025-09-09 DOI: 10.1016/j.imlet.2025.107084

Noriyuki Kitagawa , Nobuko Kitagawa , Ayaka Kobayashi , Takuro Okamura , Masahide Hamaguchi , Michiaki Fukui

Pancreatic islet antigen-specific autoreactive T cells are involved in inflammation in slowly progressive insulin-dependent diabetes mellitus (SPIDDM). Pancreatic islet antigens, such as glutamic acid decarboxylase 65 (GAD), insulinoma-associated protein 2 (IA-2), and insulin, are associated with SPIDDM. However, the association between pancreatic islet antigen-specific T cells and SPIDDM incidence remains unclear.

We aimed to identify the characteristics of pancreatic islet antigen autoreactive T cells in Japanese patients with SPIDDM.

Peripheral blood mononuclear cells were obtained from Japanese patients with type 1 diabetes mellitus (T1DM) enrolled in our diabetic cohort study. An ex vivo cytokine assay using overlapping peptides of GAD, IA-2, and insulin was performed. The production of tumor necrosis factor-alpha (TNF-α) by CD4⁺ T cells and the fractions of TNF-α⁺ CD4⁺ T cell fractions were measured by fluorescence-activated cell sorting.

The %parent of TNF-α⁺ CD4⁺ T cells and the effector memory TNF-α⁺ CD4⁺ T cells increased after stimulation with overlapping GAD and IA-2 peptides. The response to overlapping peptides was varied among individual SPIDDM case. Response to overlapping peptides of GAD, IA-2, and insulin were observed in each group of T1DM.

Islet antigen-specific autoreactive TNF-α⁺ CD4⁺ T cells from Japanese patients with SPIDDM were activated by overlapping GAD and IA-2 peptides.

胰岛抗原特异性自身反应性T细胞参与缓慢进展型胰岛素依赖型糖尿病（SPIDDM）的炎症。胰岛抗原，如谷氨酸脱羧酶65 （GAD）、胰岛素瘤相关蛋白2 （IA-2）和胰岛素，与SPIDDM有关。然而，胰岛抗原特异性T细胞与SPIDDM发病率之间的关系尚不清楚。我们的目的是确定日本SPIDDM患者胰岛抗原自身反应性T细胞的特征。我们的糖尿病队列研究从日本1型糖尿病患者（T1DM）中获得外周血单个核细胞。使用GAD， IA-2和胰岛素的重叠肽进行体外细胞因子测定。采用荧光活化细胞分选法检测CD4 + T细胞产生肿瘤坏死因子α (TNF-α)和TNF-α + CD4 + T细胞组分。TNF-α + CD4 + T细胞和效应记忆TNF-α + CD4 + T细胞的%亲本在GAD和IA-2肽重叠刺激后增加。不同的SPIDDM病例对重叠肽的反应不同。观察各组T1DM患者对GAD、IA-2和胰岛素重叠肽的反应。来自日本SPIDDM患者的胰岛抗原特异性自反应性TNF-α + CD4+ T细胞被重叠的GAD和IA-2肽激活。

{"title":"Analysis of islet antigen-specific autoreactive T cells from Japanese patients with slowly progressive insulin-dependent diabetes mellitus","authors":"Noriyuki Kitagawa , Nobuko Kitagawa , Ayaka Kobayashi , Takuro Okamura , Masahide Hamaguchi , Michiaki Fukui","doi":"10.1016/j.imlet.2025.107084","DOIUrl":"10.1016/j.imlet.2025.107084","url":null,"abstract":"<div><div>Pancreatic islet antigen-specific autoreactive T cells are involved in inflammation in slowly progressive insulin-dependent diabetes mellitus (SPIDDM). Pancreatic islet antigens, such as glutamic acid decarboxylase 65 (GAD), insulinoma-associated protein 2 (IA-2), and insulin, are associated with SPIDDM. However, the association between pancreatic islet antigen-specific T cells and SPIDDM incidence remains unclear.</div><div>We aimed to identify the characteristics of pancreatic islet antigen autoreactive T cells in Japanese patients with SPIDDM.</div><div>Peripheral blood mononuclear cells were obtained from Japanese patients with type 1 diabetes mellitus (T1DM) enrolled in our diabetic cohort study. An <em>ex vivo</em> cytokine assay using overlapping peptides of GAD, IA-2, and insulin was performed. The production of tumor necrosis factor-alpha (TNF-α) by CD4⁺ T cells and the fractions of TNF-α⁺ CD4⁺ T cell fractions were measured by fluorescence-activated cell sorting.</div><div>The %parent of TNF-α⁺ CD4⁺ T cells and the effector memory TNF-α⁺ CD4⁺ T cells increased after stimulation with overlapping GAD and IA-2 peptides. The response to overlapping peptides was varied among individual SPIDDM case. Response to overlapping peptides of GAD, IA-2, and insulin were observed in each group of T1DM.</div><div>Islet antigen-specific autoreactive TNF-α⁺ CD4<sup>+</sup> T cells from Japanese patients with SPIDDM were activated by overlapping GAD and IA-2 peptides.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107084"},"PeriodicalIF":2.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039976","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