Immunology letters最新文献_第7页

B cells are major players in cancer immunity B细胞是癌症免疫的主要参与者。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-07-30 DOI: 10.1016/j.imlet.2025.107064

Théo Bouloudani , Guilhem Pupier , Catherine Sautès-Fridman , Wolf Herman Fridman

The discovery of Tertiary Lymphoid Structures (TLS) within tumors has reshaped our understanding of cancer immunity. Unlike the classical view that immune responses are solely initiated in lymph nodes, TLS, ectopic lymphoid aggregates resembling secondary lymphoid organs, can form in the tumor microenvironment (TME). These structures contain T cells, B cells, dendritic cells (DC) presenting antigenic peptides to T cells in the T cell zone of TLS, and follicular dendritic cells (FDC) which are stromal cells involved in the formation of germinal centers (GCs) and presenting antigens, under the form of immune complexes, to B cells. Mature TLS with GCs support B cell differentiation into antibody-producing plasma cells (PCs). Clinical studies reveal that TLS presence correlates with improved survival and response to immunotherapy across multiple cancers, including melanoma, NSCLC, and renal cell carcinoma. Notably, B cells within TLS undergo clonal expansion, somatic hypermutation, and isotype switching, generating tumor-reactive antibodies (IgG, IgA). IgG-opsonized tumor cells can be eliminated by macrophages or NK cells via antibody-dependent cell mediated cytotoxicity or apoptosis by macrophages via antibody-dependent phagocytosis whereas IgA may have dual roles, sometimes promoting immunosuppression. Additionally, B cells enhance antigen presentation to T cells, amplifying anti-tumor responses. Emerging strategies aim to induce TLS formation (e.g., via CXCL13, lymphotoxins…) or harness B cells for adoptive therapies. Future research should clarify tumor-specific antibody targets and optimize TLS induction to enhance immunotherapy.

In summary, TLS and B cells are pivotal in shaping anti-tumor immunity, offering novel biomarkers and therapeutic avenues for cancer treatment.

肿瘤内三级淋巴结构（TLS）的发现重塑了我们对癌症免疫的理解。传统观点认为免疫反应仅在淋巴结中启动，但与此不同的是，肿瘤微环境（TME）中也可以形成类似次级淋巴器官的异位淋巴聚集体TLS。这些结构包括T细胞、B细胞、树突状细胞（DC）和滤泡树突状细胞（FDC），后者是参与生发中心（GCs）形成的基质细胞，并以免疫复合物的形式向B细胞呈递抗原。成熟的带有GCs的TLS支持B细胞向产生抗体的浆细胞（PCs）分化。临床研究表明，TLS的存在与多种癌症（包括黑色素瘤、非小细胞肺癌和肾细胞癌）的生存率和免疫治疗反应的改善有关。值得注意的是，TLS中的B细胞经历克隆扩增、体细胞超突变和同型转换，产生肿瘤反应性抗体（IgG, IgA）。igg活化的肿瘤细胞可通过抗体依赖细胞介导的细胞毒性被巨噬细胞或NK细胞清除或通过抗体依赖吞噬被巨噬细胞凋亡，而IgA可能具有双重作用，有时促进免疫抑制。此外，B细胞增强抗原向T细胞的呈递，增强抗肿瘤反应。新兴策略旨在诱导TLS形成（例如，通过CXCL13，淋巴毒素…）或利用B细胞进行过继治疗。未来的研究应明确肿瘤特异性抗体靶点，优化TLS诱导以增强免疫治疗。综上所述，TLS和B细胞在形成抗肿瘤免疫中起着关键作用，为癌症治疗提供了新的生物标志物和治疗途径。

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引用次数: 0

Space immunology: Unraveling immune system dysregulation in long-duration spaceflight and its implications for earth-based autoimmune and inflammatory diseases 太空免疫学：揭示长时间太空飞行中的免疫系统失调及其对地球自身免疫性和炎症性疾病的影响。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-07-25 DOI: 10.1016/j.imlet.2025.107063

Muhammad Umar , Muhammad Talha

引用次数: 0

Navigating challenges of aGvHD predictive biomarkers in αβhaplo-HSCT recipients: Still waiting for MAGIC to happen aGvHD预测生物标志物在αβ单倍造血干细胞受体中的应用：仍在等待奇迹的发生。

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-07-16 DOI: 10.1016/j.imlet.2025.107062

Raul Montiel-Esparza, Isobel Hawes, Rhonda Perriman, Giulia Barbarito, Linda Oppizzi, David Shyr, Laurel Kent, Zhenyu Yao, Alice Bertaina

The validated Mount Sinai Acute graft-versus-host disease (aGvHD) International Consortium (MAGIC) algorithm and biomarker panels did not predict aGvHD occurrence or severity in pediatric αβT-cell/CD19 B-cell depleted haploidentical hematopoietic stem cell transplant (αβhaplo-HSCT) recipients. These findings suggest distinct aGvHD biology in the αβhaplo-HSCT setting, supporting the need for tailored biomarker studies in this unique transplant platform.

经验证的西奈山急性移植物抗宿主病（aGvHD）国际联盟（MAGIC）算法和生物标志物小组不能预测儿童αβ t细胞/CD19 b细胞缺失的单倍同型造血干细胞移植（αβ单倍同型造血干细胞移植）受体中aGvHD的发生或严重程度。这些发现表明，αβ单倍体hsct环境中aGvHD具有独特的生物学特性，支持在这种独特的移植平台中进行定制生物标志物研究的必要性。

引用次数: 0

Genetic and transcriptional dysregulation of innate antiviral immune pathways in type 1 diabetes 1型糖尿病先天抗病毒免疫途径的遗传和转录失调

IF 3.3 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-07-13 DOI: 10.1016/j.imlet.2025.107060

Mia Ø Mønsted , Kristina Pedersen , Mathias H. Jensen , Simranjeet Kaur , Sofía C. Sustacha , Laurits J. Holm , Karsten Buschard , Flemming Pociot , Martin Haupt-Jorgensen

Innate antiviral immune pathways (InAIPs) are dysregulated in islets of type 1 diabetes (T1D) patients, implying how enterovirus might contribute to beta-cell autoimmunity. However, it is unclear whether similar dysregulation occurs in the intestine, contributing to pathologies like barrier dysfunction. Thus, we used a published genome-wide association study to identify polymorphisms in intestinal permeability and InAIP genes. We compared female prediabetic non-obese diabetic (NOD) and C57BL/6 mice and their jejunal epithelial RNA profile by GeneChip analysis. The potential link between dysregulation of InAIP genes and increased intestinal permeability was assessed by measuring trans-epithelial electrical resistance in intestinal Caco-2 cells upon R837 toll-like receptor 7 stimulation. There was genetic predisposition to T1D among intestinal permeability genes. However, InAIP genes contained more promising T1D-associated polymorphisms, especially for TNFA, OAS3, PIGR, CD55, NOD2, and IFIH1. Comparing prediabetic NOD with C57BL/6 mice revealed age-dependent dysregulation of several InAIP genes (Ifih1, Rnase1 etc.) in jejunum. Lastly, mimicking an enterovirus infection with R837 stimulation of Caco-2 cells increased intestinal permeability. We demonstrate genetic and transcriptional dysregulation of InAIPs in T1D and their potential involvement in intestinal barrier dysfunction, providing new clues to the disease-manifesting mechanisms of enterovirus infection.

先天抗病毒免疫途径（InAIPs）在1型糖尿病（T1D）患者胰岛中失调，暗示肠病毒可能有助于β细胞自身免疫。然而，尚不清楚类似的失调是否发生在肠道中，从而导致屏障功能障碍等病理。因此，我们使用已发表的全基因组关联研究来鉴定肠通透性和InAIP基因的多态性。我们通过基因芯片分析比较了雌性糖尿病前期非肥胖糖尿病（NOD）和C57BL/6小鼠及其空肠上皮RNA谱。通过测量肠Caco-2细胞在R837 toll样受体7刺激下的跨上皮电阻，评估InAIP基因失调与肠通透性增加之间的潜在联系。肠通透性基因间存在T1D的遗传易感性。然而，InAIP基因包含更多有希望的t1d相关多态性，特别是TNFA、OAS3、PIGR、CD55、NOD2和IFIH1。将糖尿病前期NOD与C57BL/6小鼠进行比较，发现空肠中多个InAIP基因（Ifih1， Rnase1等）的年龄依赖性失调。最后，用R837刺激Caco-2细胞模拟肠道病毒感染，增加肠道通透性。我们证明了T1D中InAIPs的遗传和转录失调及其可能参与肠道屏障功能障碍，为肠道病毒感染的疾病表现机制提供了新的线索。

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引用次数: 0

Elevated ascitic interleukin-36 receptor antagonist mediates CD8+ T cell exhaustion in vitro in liver cirrhotic patients with spontaneous bacterial peritonitis 腹水白细胞介素-36受体拮抗剂升高介导肝硬化合并自发性细菌性腹膜炎患者体外CD8+ T细胞衰竭

IF 3.3 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-07-11 DOI: 10.1016/j.imlet.2025.107061

Lanlan Yang, Siqi Liu, Chen Qiu, Qian Zhang, Chuanhui Zhang, Zhenjing Jin

Interleukin-36 (IL-36) signaling pathway plays an important regulatory role in inflammatory and infectious diseases. However, the modulatory function of IL-36 in CD8⁺ T cells that are involved in liver cirrhosis with spontaneous bacterial peritonitis (SBP) has not been understood. Sixty-five liver cirrhotic patients (42 untainted ascites and 23 SBP patients) and 20 controls were included. IL-36 levels were measured by ELISA. CD8⁺ T cells were purified from ascites, and were stimulated with IL-36 receptor antagonist (IL-36RA). CD8⁺ T cells were co-cultured with HepG2 cells in direct contact and indirect contact manners. Target cell death and cytotoxic molecules levels were investigated to assess CD8⁺ T cell cytotoxicity. The immune-checkpoint molecules expressions on CD8⁺ T cells were measured by flow cytometry. There were no significant differences in IL-36alpha, IL-36beta, or IL-36gamma levels between untainted ascites and SBP patients. SBP patients had increased ascitic IL-36RA, which positively correlated with alanine aminotransferase and ascitic neutrophil count. IL-36RA stimulation did not affect CD8⁺ T cell proliferation, but dampened CD8⁺ T cell-induced cell death and proinflammatory cytokine secretions. Perforin and granzyme B productions were down-regulated in direct contact manner. IL-36RA stimulation promoted immune-checkpoint molecules expressions on CD8⁺ T cells. The present findings revealed that elevated ascitic IL-36RA might inhibit ascitic CD8⁺ T cell cytotoxicty in liver cirrhotic patients with SBP.

白细胞介素-36 （IL-36）信号通路在炎症和感染性疾病中起着重要的调节作用。然而，IL-36在参与肝硬化合并自发性细菌性腹膜炎（SBP）的CD8+ T细胞中的调节功能尚不清楚。65例肝硬化患者（42例未污染腹水患者和23例收缩压患者）和20例对照组。ELISA法检测IL-36水平。从腹水中纯化CD8+ T细胞，用IL-36受体拮抗剂（IL-36RA）刺激。CD8+ T细胞与HepG2细胞采用直接接触和间接接触两种方式共培养。研究靶细胞死亡和细胞毒分子水平以评估CD8+ T细胞的细胞毒性。流式细胞术检测免疫检查点分子在CD8+ T细胞上的表达。在未受污染的腹水和SBP患者之间，il -36 α、il -36 β或il -36 γ水平无显著差异。SBP患者腹水IL-36RA升高，与丙氨酸转氨酶和腹水中性粒细胞计数呈正相关。IL-36RA刺激不影响CD8+ T细胞增殖，但抑制CD8+ T细胞诱导的细胞死亡和促炎细胞因子分泌。穿孔素和颗粒酶B的产生以直接接触的方式下调。IL-36RA刺激可促进CD8+ T细胞免疫检查点分子的表达。本研究结果表明，升高的腹水IL-36RA可能抑制肝硬化合并SBP患者腹水CD8+ T细胞毒性。

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引用次数: 0

The CSF transcriptome in adults with pneumococcal meningitis reveals compartmentalised host inflammatory responses associated with mortality 成人肺炎球菌脑膜炎的脑脊液转录组揭示了与死亡率相关的区隔宿主炎症反应。

IF 3.3 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-07-07 DOI: 10.1016/j.imlet.2025.107059

José Afonso Guerra-Assunção , Probir Chakravarty , Gabriele Pollara , Cristina Venturini , Veronica S Mlozowa , Brigitte Denis , Mulinda Nyirenda , David G Lalloo , Mahdad Noursadeghi , Jeremy S Brown , Robert S Heyderman , Emma C Wall

Pneumococcal meningitis (PM) has persistently poor clinical outcomes, especially in sub-Saharan Africa. To better characterise the inflammatory response and identify factors associated with mortality we compared paired peripheral blood and cerebrospinal fluid (CSF) transcriptomes before the initiation of antibiotics in Malawian adults with proven PM.

Blood transcriptional profiles were obtained in 28 patients with PM, with simultaneous paired with CSF profiles available for 13 patients. 15/28 (52 %) patients died. Comparison of the transcriptome between CSF and blood compartments showed upregulation of 2293 differentially expressed genes in CSF and 909 in blood; enriched pathways in CSF included inflammasome activity and neutrophil migration/activation, contrasting with enrichment for pathways including platelet and endothelial activation, cell cycle, cytokine release and oxidative stress in the blood transcriptome. Comparison of CSF profiles between survivors and non-survivors revealed 1829 differentially expressed genes. Non-survivor CSF was enriched for multiple innate inflammatory pathways, including IL-17A and Type 1 interferons and proteolysis. In contrast, minimal transcriptomic differences between outcome groups were detected in blood.

Inflammation in PM is characterised by compartmentalised responses in blood and CSF. Poorer outcomes are associated with an dysregulated innate immune host response to S. pneumoniae in the CSF compartment.

肺炎球菌脑膜炎（PM）的临床结果一直很差，特别是在撒哈拉以南非洲。为了更好地表征炎症反应并确定与死亡率相关的因素，我们比较了马拉维成年确诊PM患者在开始使用抗生素之前的成对外周血和脑脊液（CSF）转录组。在28例PM患者中获得了血液转录谱，同时配对了13例患者的CSF谱。15/28（52%）患者死亡。脑脊液与血室的转录组比较显示，脑脊液中有2293个差异表达基因上调，血室中有909个差异表达基因上调；脑脊液中富集的途径包括炎性体活性和中性粒细胞迁移/活化，而血液转录组中富集的途径包括血小板和内皮活化、细胞周期、细胞因子释放和氧化应激。幸存者和非幸存者的脑脊液谱比较发现了1829个差异表达基因。非幸存者CSF富含多种先天性炎症途径，包括IL-17A和1型干扰素和蛋白水解。相比之下，在血液中检测到结果组之间的转录组差异很小。PM炎症的特征是血液和脑脊液的区隔反应。较差的结果与先天性免疫宿主对脑脊液室肺炎链球菌反应失调有关。

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引用次数: 0

Unraveling the biological potential of skin fibroblast: responses to TNF-α, highlighting intracellular signaling pathways and secretome 揭示皮肤成纤维细胞的生物学潜能：对TNF-α的反应，突出细胞内信号通路和分泌组。

IF 3.3 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-07-04 DOI: 10.1016/j.imlet.2025.107057

Carlota Pascoal , Pedro Granjo , Patrícia Mexia , Diana Gallego , Rita Adubeiro Lourenço , Shally Sharma , Bélen Pérez , Margarida Castro-Caldas , Ana Rita Grosso , Vanessa dos Reis Ferreira , Paula Alexandra Videira

Objective

In this study, we examined the molecular response of human skin fibroblasts to an inflammatory cytokine to evaluate their suitability as models for immunopathology research.

Methods

Skin fibroblasts were stimulated with tumour necrosis factor (TNF)-α, and the transcriptome was profiled via RNA-Seq. The differentially expressed genes were screened to predict immunological pathways and interactions. The cytokines and signaling pathways were validated at protein level. Similarly to immune cells, TNF-α caused transcriptional and transductional changes in fibroblasts.

Results

Functional analysis revealed significant enrichment of TNF-α signaling and cell chemotaxis (normalized enrichment score = 2.59 and 3.42). We also detected enrichment of nuclear factor kappa B (NF-κB) target genes and NF-kB activation, confirmed by complete protein degradation of its inhibitor IκBa (p = 0.0019). The MAPK/ERK and p38 MAPK pathways were also activated. Finally, we observed significant secretion of proinflammatory cytokines and chemokines, such as interleukin 6 (p = 0.02), CXCL8 (p = 0.027), CCL2 (p = 0.028) and CCL5 (p = 0.016).

Conclusion

This study advances the biological understanding of skin fibroblast responses to TNF-α, revealing their intracellular pathways and secretome. It discloses techniques for leveraging fibroblasts' potential as in vitro models to identify inflammatory drivers, particularly when alternative models are inaccessible.

目的：在本研究中，我们检测了人皮肤成纤维细胞对炎症细胞因子的分子反应，以评估其作为免疫病理学研究模型的适用性。方法：用肿瘤坏死因子(TNF)-α刺激皮肤成纤维细胞，通过RNA-Seq分析其转录组。筛选差异表达基因以预测免疫途径和相互作用。细胞因子和信号通路在蛋白水平上得到验证。与免疫细胞类似，TNF-α引起成纤维细胞的转录和转导变化。结果：功能分析显示TNF-α信号和细胞趋化性显著富集（归一化富集评分分别为2.59和3.42）。我们还检测到核因子κB （NF-κB）靶基因的富集和NF- kb的活化，证实了其抑制剂i -κ ba的完全蛋白降解（p=0.0019）。MAPK/ERK和p38 MAPK通路也被激活。最后，我们观察到促炎细胞因子和趋化因子的显著分泌，如白细胞介素6 （p=0.02）、CXCL8 （p=0.027）、CCL2 （p=0.028）和CCL5 （p=0.016）。结论：本研究促进了对皮肤成纤维细胞对TNF-α反应的生物学认识，揭示了其细胞内通路和分泌组。它揭示了利用成纤维细胞作为体外模型的潜力来识别炎症驱动因素的技术，特别是当无法获得替代模型时。

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引用次数: 0

Splenomegaly in CVID patients associates with CMV replication and alterations of immune cells and functions CVID患者脾肿大与巨细胞病毒复制、免疫细胞和功能改变有关。

IF 3.3 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-07-04 DOI: 10.1016/j.imlet.2025.107058

Luca Marri , Paola Contini , Federico Ivaldi , Chiara Schiavi , Ottavia Magnani , Chiara Vassallo , Andrea Guastalla , Noemi Traversone , Davide Deraco , Claudia Angelini , Genny Del Zotto , Raffaele De Palma , Andrea De Maria

Background

Splenomegaly represents a frequent non-infectious manifestation in Common Variable Immunodeficiency (CVID) and associates with specific clinical and immunophenotypic characteristics.

Objective

To investigate the association between splenomegaly, infections, and immunophenotype in CVID patients.

Methods

A cohort of 32 CVID patients (13 with splenomegaly) was enrolled. Infectious workup encompassed a detailed medical history and data derived from routine diagnostic assessments including specific virological analysis of blood and stool samples, and QuantiFERON assay for tuberculosis. Immunophenotype was assessed by multiparametric flow cytometry. Statistical analyses were performed using Prism and Jamovi software.

Results

CMV viraemia was detected in 40 % of splenomegalic CVID (sCVID) and was absent in non-sCVID patients. Of all infectious agents, CMV was the only one associated with splenomegaly (p = 0.009). The inclusion of CMV replication as a causative factor for splenomegaly in CVID is in line with the knowledge that splenomegaly is a hallmark of acute CMV infection and could help explain in the present CVID cohort 75 % of otherwise unexplained splenomegalies. Flow cytometric analysis in sCVID vs. non-sCVID confirmed decreases in NK cell numbers and activation, in circulating inflammatory precursors (Lin⁻CD16⁺), and increased T cell activation as defined by HLA-DR/CD69/CD38 expression.

Conclusion

Splenomegaly in CVID patients may associate also with CMV replication. The combined identification in CMV⁺ sCVID of NK cell, inflammatory precursor and T cell imbalances suggests a possible combined cellular defect at precursor level in a subset of sCVID patients. When integrated into everyday clinical management, CMV viraemia could become a useful additional parameter for patient characterization and stratification.

背景：脾肿大是常见的非感染性免疫缺陷（CVID）的表现，与特定的临床和免疫表型特征有关。目的：探讨CVID患者脾肿大、感染与免疫表型的关系。方法：入选32例CVID患者（其中脾肿大13例）。传染病检查包括详细的病史和来自常规诊断评估的数据，包括对血液和粪便样本的特定病毒学分析，以及结核病的QuantiFERON检测。采用多参数流式细胞术评价免疫表型。采用Prism和Jamovi软件进行统计分析。结果：40%的脾大性CVID （sCVID）患者检测到巨细胞病毒血症，而非sCVID患者不存在巨细胞病毒血症。在所有感染因子中，巨细胞病毒是唯一与脾肿大相关的感染因子（p=0.009）。将巨细胞病毒复制作为CVID中脾肿大的一个致病因素，这与脾肿大是急性巨细胞病毒感染的标志这一认识是一致的，并且可以帮助解释目前CVID队列中75%的其他原因不明的脾肿大。流式细胞分析证实，sCVID患者与非sCVID患者相比，NK细胞数量和活化减少，循环炎症前体（Lin-CD16+）减少，T细胞活化增加（由HLA-DR/CD69/CD38表达定义）。结论：CVID患者脾肿大可能与巨细胞病毒复制有关。CMV+ sCVID中NK细胞、炎症前体细胞和T细胞失衡的联合鉴定表明，在sCVID患者的一个亚群中，可能存在前体细胞水平的联合细胞缺陷。当整合到日常临床管理时，巨细胞病毒血症可能成为患者特征和分层的有用附加参数。

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引用次数: 0

Immune cells and functions in patients with restless legs syndrome 不宁腿综合征患者的免疫细胞和功能。

IF 3.3 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-06-30 DOI: 10.1016/j.imlet.2025.107056

Aysenur Kokoglu , Ayse Engin , Metin Yusuf Gelmez , Esin Aktas Cetin , Gulcin Benbir Senel , Derya Karadeniz , Gunnur Deniz

Restless legs syndrome (RLS) is a sleep-related disorder, and some evidence suggests that inflammation contributes to its pathophysiology. This study aimed to investigate the relationship between RLS and immune cells.

Fourteen RLS patients, and 10 healthy subjects were included in the study. The percentages of T, B, natural killer (NK), natural killer T (NKT) and innate lymphoid cells (ILCs) were analyzed, along with intracellular levels of interferon-gamma (IFN-γ), interleukin (IL)-6, IL-10, and IL-13 in T, B and NK cells. Additionally, CD8⁺ T and NK cell cytotoxic activities were assessed using flow cytometry. Plasma levels of IFN-γ, tumor necrosis factor-alpha (TNF-α), IL-2, IL-4, IL-6, IL-10, and IL-13 were evaluated with bead-based soluble molecule assay.

Compared to healthy subjects, the ratio of ILC-1 subset and IL-13⁺CD4⁺ T cells were significantly increased in RLS patients, while the levels of ILC-2 subset were significantly decreased. When the NK cell cytotoxic activity of RLS patients was evaluated, it was found that the NK cell perforin levels were lower than healthy subjects. Plasma IL-13 levels were also significantly elevated in RLS patients compared to healthy individuals.

These findings suggest that both innate and adaptive immune responses may play a role in RLS pathophysiology. Alterations in ILC subsets, along with elevated IL-13, IL-10, and IL-6 levels, as well as NK and CD8⁺ T cell cytotoxic activity, indicate that immune dysregulation might contribute to the disease mechanism. Furthermore, the observed correlation between efficient sleep and immune markers highlights the potential role of immune system modulation in RLS management.

不宁腿综合征（RLS）是一种与睡眠有关的疾病，一些证据表明炎症有助于其病理生理。本研究旨在探讨RLS与免疫细胞的关系。本研究纳入14例RLS患者和10例健康受试者。分析T、B、自然杀伤细胞（NK）、自然杀伤T细胞（NKT）和先天淋巴样细胞（ILCs）的百分比，以及T、B和NK细胞内干扰素-γ (IFN-γ)、白细胞介素(IL)-6、IL-10、IL-13的水平。此外，利用流式细胞术评估CD8+ T和NK细胞的细胞毒活性。采用珠状可溶性分子法检测血浆中IFN-γ、肿瘤坏死因子α (TNF-α)、IL-2、IL-4、IL-6、IL-10和IL-13的水平。与健康受试者相比，RLS患者ILC-1亚群和IL-13+ CD4+ T细胞比例显著升高，ILC-2亚群水平显著降低。对RLS患者NK细胞的细胞毒活性进行评价，发现NK细胞穿孔素水平低于健康人。与健康个体相比，RLS患者血浆IL-13水平也显著升高。这些发现提示先天性和适应性免疫反应可能在RLS的病理生理中发挥作用。ILC亚群的改变，以及IL-13、IL-10和IL-6水平的升高，以及NK和CD8+ T细胞的细胞毒性活性，表明免疫失调可能与疾病机制有关。此外，观察到的有效睡眠与免疫标记物之间的相关性突出了免疫系统调节在RLS管理中的潜在作用。

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引用次数: 0

Alterations in chemokine receptor-ligand interactions and costimulatory molecules in DC-NK crosstalk: A novel therapeutic approach for pemphigus vulgaris 趋化因子受体-配体相互作用和DC-NK串扰中共刺激分子的改变：一种治疗寻常型天疱疮的新方法。

IF 3.3 4区医学 Q3 IMMUNOLOGY

Immunology letters

Pub Date : 2025-06-27 DOI: 10.1016/j.imlet.2025.107055

Vishakha Hooda , Divya Sharma , Ashu Singh , Dayasagar Das , Somesh Gupta , Sudheer Arava , Alpana Sharma

Innate immune cells, particularly natural killer (NK) cells and dendritic cells (DCs), play a crucial role in the immunopathogenesis of Pemphigus Vulgaris (PV), an autoimmune blistering disorder. Dysregulation of these innate cells can lead to significant consequences in the adaptive immune response, contributing to disease progression. This study investigates the crosstalk between NK cells and DCs as a potential therapeutic target for PV. Our findings reveal an increased frequency of DCs (mDCs and pDCs) and NK cells (CD56^dim and CD56^bright) in the peripheral circulation of PV patients. NK cells exhibited elevated granzyme activity and IFNγ production, while DCs displayed enhanced phagocytic capabilities. In vitro, we observed upregulated mRNA expression of potentially interacting co-stimulatory markers (CD40 and CD80) and chemokines (CXCL10 and CXCL8) in DCs, alongside increased expression of their corresponding receptors (CD40L, CD80L, CXCR3, and CXCR1) on NK cells. Lesional tissues from PV patients also showed heightened expression of these receptor-ligand pairs. Co-culture experiments further demonstrated increased granzyme activity in NK cells and enhanced phagocytosis in DCs, however, blocking of CXCR3 resulted in decreased granzyme activity, suggesting a functional modulation through their interaction. These findings highlight the significant role of NK-DC crosstalk in PV pathogenesis and suggest that targeting this interaction could offer a novel therapeutic strategy to modulate immune responses in PV, offering the potential for more effective treatment approaches.

先天免疫细胞，特别是自然杀伤细胞（NK）和树突状细胞（dc），在天疱疮（PV）的免疫发病机制中起着至关重要的作用，这是一种自身免疫性起泡疾病。这些先天细胞的失调可导致适应性免疫反应的显著后果，促进疾病进展。本研究探讨了NK细胞和dc之间的串扰作为PV的潜在治疗靶点。我们的研究结果显示PV患者外周血中dc （mDCs和pDCs）和NK细胞（CD56dim和CD56bright）的频率增加。NK细胞表现出颗粒酶活性和IFNγ产生的升高，而dc细胞表现出增强的吞噬能力。在体外，我们观察到dc中可能相互作用的共刺激标记物（CD40和CD80）和趋化因子（CXCL10和CXCL8） mRNA表达上调，同时NK细胞上相应受体（CD40L、CD80L、CXCR3和CXCR1）表达增加。PV患者的病变组织也表现出这些受体-配体对的高表达。共培养实验进一步表明，NK细胞颗粒酶活性增加，dc细胞吞噬能力增强，然而，阻断CXCR3导致颗粒酶活性降低，表明它们通过相互作用进行功能调节。这些发现强调了NK-DC串扰在PV发病机制中的重要作用，并表明靶向这种相互作用可能提供一种新的治疗策略来调节PV的免疫反应，为更有效的治疗方法提供了潜力。

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引用次数: 0