Journal of autoimmunity最新文献

{"title":"Outcome and prognosis of isolated carotid vasculitis","authors":"A. Hankard ,&nbsp;G. Maalouf ,&nbsp;J. Laouni ,&nbsp;O. Espitia ,&nbsp;C. Agard ,&nbsp;H. De Boysson ,&nbsp;A. Aouba ,&nbsp;K. Sacré ,&nbsp;T. Papo ,&nbsp;G. Leroux ,&nbsp;M. Vautier ,&nbsp;A.C. Desbois ,&nbsp;F. Domont ,&nbsp;A. Le Joncour ,&nbsp;A. Mirouse ,&nbsp;L. Chiche ,&nbsp;Y. Skaff ,&nbsp;J. Gaudric ,&nbsp;S. Boussouar ,&nbsp;A. Redheuil ,&nbsp;D. Saadoun","doi":"10.1016/j.jaut.2024.103242","DOIUrl":"10.1016/j.jaut.2024.103242","url":null,"abstract":"<div><h3>Objective</h3><p>To assess the prognosis and outcome of patients with isolated carotid vasculitis.</p></div><div><h3>Methods</h3><p>We performed a retrospective multicenter study of 36 patients (median age at diagnosis was 37 [IQR 27–45] years and 11 [31 %] patients were men) with initial presentation as isolated carotid vasculitis. Study endpoints included vascular complications, relapses, and progression to large vessel vasculitis (i.e. Giant cell arteritis or Takayasu).</p></div><div><h3>Results</h3><p>The most frequent involvement was the left internal carotid artery (39 %), and 81 % had stenosis. After a median follow-up of 32 months [IQR 12–96], 21 (58 %) patients had a vascular event, including 31 % of new onset vascular lesions and 25 % of stroke/transient ischemic attack. Patients with stroke had less carotidynia at diagnosis (33 % vs 74 %, p = 0.046), higher significant carotid stenosis (i.e. &gt; 50 %) (89 % vs. 30 %, p = 0.026) and higher severe carotid stenosis (i.e. &gt;70 %) (67 % vs 19 %, p = 0.012), compared to those without stroke. Twenty (52 %) patients experienced relapses. High CRP at diagnosis was associated with relapses (p = 0.022). At the end of follow-up, 21 (58 %) patients were classified as having Takayasu arteritis, 13 (36 %) as isolated carotid vasculitis, and two (6 %) as giant cell arteritis.</p></div><div><h3>Conclusion</h3><p>Carotid vasculitis may occur as a topographically limited lesion and is associated with significant rate of vascular complications.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103242"},"PeriodicalIF":12.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000763/pdfft?md5=cb72b13f764e26d795452b8a2e83203a&pid=1-s2.0-S0896841124000763-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding CD4+ T cell transcriptome in giant cell arteritis: Novel pathways and altered cross-talk with monocytes","authors":"Elkyn Estupiñán-Moreno ,&nbsp;José Hernández-Rodríguez ,&nbsp;Tianlu Li ,&nbsp;Laura Ciudad ,&nbsp;Eduardo Andrés-León ,&nbsp;Laura Carmen Terron-Camero ,&nbsp;Sergio Prieto-González ,&nbsp;Georgina Espígol-Frigolé ,&nbsp;Maria C. Cid ,&nbsp;Ana Márquez ,&nbsp;Javier Martin ,&nbsp;Esteban Ballestar ,&nbsp;Lourdes Ortiz-Fernández","doi":"10.1016/j.jaut.2024.103240","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103240","url":null,"abstract":"<div><h3>Background</h3><p>Giant cell arteritis (GCA) is an immune-mediated large-vessels vasculitis with complex etiology. Although the pathogenic mechanisms remain poorly understood, a central role for CD4⁺ T cells has been demonstrated. In this context, understanding the transcriptome dysregulation in GCA CD4⁺ T cells will yield new insights into its pathogenesis.</p></div><div><h3>Methods</h3><p>Transcriptome analysis was conducted on CD4⁺ T cells from 70 patients with GCA with different disease activity and treatment status (active patients before treatment and patients in remission with and without glucocorticoid treatment), and 28 healthy controls. The study also evaluated potential impacts of DNA methylation on gene expression alterations and assessed cross-talk with CD14⁺ monocytes.</p></div><div><h3>Results</h3><p>This study has uncovered a substantial number of genes and pathways potentially contributing to the pathogenicity of CD4⁺ T cells in GCA. Specifically, CD4⁺ T cells from GCA patients with active disease exhibited altered expression levels of genes involved in multiple immune-related processes, including various interleukins (IL) signaling pathways. Notably, IL-2, a decisive interleukin for regulatory T cells homeostasis, was among the most significant. Additionally, impaired apoptotic pathways appear crucial in GCA development. Our findings also suggest that histone-related epigenetic pathways may be implicated in promoting an inflammatory phenotype in GCA active patients. Finally, our study observed altered signaling communication, such as the Jagged-Notch signaling, between CD4⁺ T cells and monocytes that could have pathogenic relevance in GCA.</p></div><div><h3>Conclusions</h3><p>Our study suggests the participation of novel cytokines and pathways and the occurrence of a disruption of monocyte-T cell crosstalk driving GCA pathogenesis.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103240"},"PeriodicalIF":12.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S089684112400074X/pdfft?md5=216e4146e815fa302f669587354479a0&pid=1-s2.0-S089684112400074X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140947434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective activation of naïve B cells with unique epitope specificity shapes autoantibody formation in celiac disease","authors":"Saykat Das ,&nbsp;Jorunn Stamnaes ,&nbsp;Lene S. Høydahl ,&nbsp;Christine Skagen ,&nbsp;Knut E.A. Lundin ,&nbsp;Jørgen Jahnsen ,&nbsp;Ludvig M. Sollid ,&nbsp;Rasmus Iversen","doi":"10.1016/j.jaut.2024.103241","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103241","url":null,"abstract":"<div><p>Many antibody responses induced by infection, vaccination or autoimmunity show signs of convergence across individuals with epitope-dependent selection of particular variable region gene segments and complementarity determining region 3 properties. However, not much is known about the relationship between antigen-specific effector cells and antigen-specific precursors present in the naïve B-cell repertoire. Here, we sought to address this relationship in the context of celiac disease, where there is a stereotyped autoantibody response against the enzyme transglutaminase 2 (TG2). By generating TG2-specific monoclonal antibodies from both duodenal plasma cells and circulating naïve B cells, we demonstrate a discord between the naïve TG2-specific repertoire and the cells that are selected for autoantibody production. Hence, the naïve repertoire does not fully reflect the epitope preference and gene usage observed for memory B cells and plasma cells. Instead, distinct naïve B cells that target particular TG2 epitopes appear to be selectively activated at the expense of TG2-binding B cells targeting other epitopes.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103241"},"PeriodicalIF":12.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000751/pdfft?md5=1f149a036f2ec8b6d91aed09310c920c&pid=1-s2.0-S0896841124000751-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140947432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microchimeric cells promote production of rheumatoid arthritis-specific autoantibodies","authors":"Marie Hemon ,&nbsp;Mathilde Giassi ,&nbsp;Yoan Ghaffar ,&nbsp;Marielle Martin ,&nbsp;Jean Roudier ,&nbsp;Isabelle Auger ,&nbsp;Nathalie C. Lambert","doi":"10.1016/j.jaut.2024.103238","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103238","url":null,"abstract":"<div><h3>Background</h3><p>Women are more likely to develop autoimmune diseases than men. Contribution from microchimerism (Mc) has been proposed, as women naturally acquire Mc from more sources than men because of pregnancy. Women with Rheumatoid Arthritis (RA) who lack RA-associated HLA alleles have been found to harbor Mc with RA-associated HLA alleles in higher amounts than healthy women in prior work. However, an immunological impact of Mc remains to be elucidated.</p></div><div><h3>Objectives</h3><p>To test the hypothesis that Mc with RA-risk associated HLA alleles can result in the production of RA-associated autoantibodies, when host genetic risk is absent.</p></div><div><h3>Methods</h3><p>DBA/2 mice are unable to produce RA-specific anti-citrullinated autoantibodies (ACPAs) after immunization with the enzyme peptidyl arginine deiminase (PAD) in a previously developed model. DBA/2 females were mated with C57BL/6 males humanized to express HLA-DR4, which is associated with RA-risk and production of ACPAs, to evaluate DR4+ fetal Mc contribution. Next, DBA/2 females born of heterozygous DR4^+/− mothers were evaluated for DR4+ Mc of maternal or littermate origin. Finally, DBA/2 females from DR4^+/− mothers were crossed with DR4⁺ males, to evaluate the contribution of any Mc source to ACPA production.</p></div><div><h3>Results</h3><p>After PAD immunization, between 20 % and 43 % of DBA/2 females (otherwise unable to produce ACPAs) had detectable ACPAs (CCP2 kit) after exposure to sources of Mc with RA-associated HLA alleles, compared to 0 % of unmated/unexposed DBA/2 females. Further the microchimeric origin of the autoantibodies was confirmed by detecting a C57BL/6-specific immunoglobulin isotype in the DBA/2 response.</p></div><div><h3>Conclusion</h3><p>Our study demonstrates that Mc cells can produce “autoantibodies” and points to a role of Mc in the biology of autoimmune diseases, including RA.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103238"},"PeriodicalIF":12.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000726/pdfft?md5=0b6fa9f0ae4d2d374217f642033309a5&pid=1-s2.0-S0896841124000726-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140947433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural IgG protects against early dissemination of vesicular stomatitis virus","authors":"Abdelrahman Elwy ,&nbsp;Hossam Abdelrahman ,&nbsp;Julia Specht ,&nbsp;Swati Dhiman ,&nbsp;Theresa Charlotte Christ ,&nbsp;Judith Lang ,&nbsp;Justa Friebus-Kardash ,&nbsp;Mike Recher ,&nbsp;Karl Sebastian Lang","doi":"10.1016/j.jaut.2024.103230","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103230","url":null,"abstract":"<div><p>Neonatal Fc receptor (FcRn) recycles immunoglobulin G, and inhibition of FcRn is used clinically for treatment of autoimmune diseases. In this work, using the vesicular stomatitis virus (VSV) mouse infection model system, we determined the role of FcRn during virus infection. While induction of neutralizing antibodies and long-term protection of these antibodies was hardly affected in FcRn deficient mice, FcRn deficiency limited the amount of natural IgG (VSV-specific) antibodies. Lack of natural antibodies (nAbs) limited early control of VSV in macrophages, accelerated propagation of virus in several organs, led to the spread of VSV to the neural tissue resulting in fatal outcomes. Adoptive transfer of natural IgG into FcRn deficient mice limited early propagation of VSV in FcRn deficient mice and enhanced survival of FcRn knockout mice. In line with this, vaccination of FcRn mice with very low dose of VSV prior to infection similarly prevented death after infection. In conclusion we determined the importance of nAbs during VSV infection. Lack of FcRn limited nAbs and thereby enhanced the susceptibility to virus infection.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103230"},"PeriodicalIF":12.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000647/pdfft?md5=da1f131444e9b6510c3b5da3b9999f53&pid=1-s2.0-S0896841124000647-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140947431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD72 is an inhibitory pattern recognition receptor that recognizes ribosomes and suppresses production of anti-ribosome autoantibody","authors":"Chizuru Akatsu ,&nbsp;Takahiro Tsuneshige ,&nbsp;Nobutaka Numoto ,&nbsp;Wang Long ,&nbsp;Toshio Uchiumi ,&nbsp;Yoshikatsu Kaneko ,&nbsp;Masatake Asano ,&nbsp;Nobutoshi Ito ,&nbsp;Takeshi Tsubata","doi":"10.1016/j.jaut.2024.103245","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103245","url":null,"abstract":"<div><p>B cell responses to nucleic acid-containing self-antigens that involve intracellular nucleic acid sensors play a crucial role in autoantibody production in SLE. CD72 is an inhibitory B cell co-receptor that down-regulates BCR signaling, and prevents the development of SLE. We previously showed that CD72 recognizes the RNA-containing self-antigen Sm/RNP, a target of SLE-specific autoantibodies, and induces B cell tolerance to Sm/RNP by specifically inhibiting B cell response to this self-antigen. Here, we address whether CD72 inhibits B cell response to ribosomes because the ribosome is an RNA-containing self-antigen and is a target of SLE-specific autoantibodies as well as Sm/RNP. We demonstrate that CD72 recognizes ribosomes as a ligand, and specifically inhibits BCR signaling induced by ribosomes. Although conventional protein antigens by themselves do not induce proliferation of specific B cells, ribosomes induce proliferation of B cells reactive to ribosomes in a manner dependent on RNA. This proliferative response is down-regulated by CD72. These results suggest that ribosomes activate B cells by inducing dual signaling through BCR and intracellular RNA sensors and that CD72 inhibits B cell response to ribosomes. Moreover, CD72^−/− but not CD72^+/+ mice spontaneously produce anti-ribosome autoantibodies. Taken together, CD72 induces B cell self-tolerance to ribosomes by recognizing ribosomes and inhibiting RNA-dependent B cell response to this self-antigen. CD72 appears to prevent development of SLE by inhibiting autoimmune B cell responses to multiple RNA-containing self-antigens. Because these self-antigens but not protein self-antigens induce RNA-dependent B cell activation, self-tolerance to RNA-containing self-antigens may require a distinct tolerance mechanism mediated by CD72.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103245"},"PeriodicalIF":12.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140947435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the 2023 ACR/EULAR antiphospholipid syndrome classification criteria in a Chinese cohort: Impact on clinical practice","authors":"Yaqing Yang ,&nbsp;Haiyue Jiang ,&nbsp;Zihan Tang ,&nbsp;Haoyu Pan,&nbsp;Honglei Liu,&nbsp;Xiaobing Cheng,&nbsp;Yutong Su,&nbsp;Junna Ye,&nbsp;Qiongyi Hu,&nbsp;Jianfen Meng,&nbsp;Huihui Chi,&nbsp;Zhuochao Zhou,&nbsp;Jinchao Jia,&nbsp;Chengde Yang,&nbsp;Hui Shi ,&nbsp;Jialin Teng ,&nbsp;Tingting Liu","doi":"10.1016/j.jaut.2024.103237","DOIUrl":"10.1016/j.jaut.2024.103237","url":null,"abstract":"<div><h3>Objectives</h3><p>To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria.</p></div><div><h3>Methods</h3><p>A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I (aβ2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria.</p></div><div><h3>Results</h3><p>The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as “probable APS”. Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aβ2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included.</p></div><div><h3>Conclusions</h3><p>The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103237"},"PeriodicalIF":12.8,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000714/pdfft?md5=9844f76d307d00c858f7d89bf1968cc1&pid=1-s2.0-S0896841124000714-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The immunopathogenesis of sarcoidosis.","authors":"Jelle Miedema, Francesco Cinetto, Anna Smed-Sörensen, Paolo Spagnolo","doi":"10.1016/j.jaut.2024.103247","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103247","url":null,"abstract":"<p><p>Sarcoidosis is a granulomatous multiorgan disease, thought to result from exposure to yet unidentified antigens in genetically susceptible individuals. The exaggerated inflammatory response that leads to granuloma formation is highly complex and involves the innate and adaptive immune system. Consecutive immunological studies using advanced technology have increased our understanding of aberrantly activated immune cells, mediators and pathways that influence the formation, maintenance and resolution of granulomas. Over the years, it has become increasingly clear that disease immunopathogenesis can only be understood if the clinical heterogeneity of sarcoidosis is taken into consideration, along with the distribution of immune cells in peripheral blood and involved organs. Most studies offer an immunological snapshot during disease course, while the cellular composition of both the circulation and tissue microenvironment may change over time. Despite these challenges, novel insights on the role of the immune system are continuously published, thus bringing the field forward. This review highlights current knowledge on the innate and adaptive immune responses involved in sarcoidosis pathogenesis, as well as the pathways involved in non-resolving disease and fibrosis development. Additionally, we describe proposed immunological mechanisms responsible for drug-induced sarcoid like reactions. Although many aspects of disease immunopathogenesis remain to be unraveled, the identification of crucial immune reactions in sarcoidosis may help identify new treatment targets. We therefore also discuss potential therapies and future strategies based on the latest immunological findings.</p>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":" ","pages":"103247"},"PeriodicalIF":12.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tfh cell-derived small extracellular vesicles exacerbate the severity of collagen-induced arthritis by enhancing B-cell responses","authors":"Jian Lu ,&nbsp;Huimin Zhou ,&nbsp;Yuxuan Chen ,&nbsp;Xueli Xia ,&nbsp;Jun Yang ,&nbsp;Jie Ma ,&nbsp;Jie Tian ,&nbsp;Shengjun Wang","doi":"10.1016/j.jaut.2024.103235","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103235","url":null,"abstract":"<div><p>Soluble components secreted by Tfh cells are critical for the germinal center responses. In this study, we investigated whether Tfh cells could regulate the B-cell response by releasing small extracellular vesicles (sEVs). Our results showed that Tfh cells promote B-cell differentiation and antibody production through sEVs and that CD40L plays a crucial role in Tfh-sEVs function. In addition, increased Tfh-sEVs were found in mice with collagen-induced arthritis (CIA). Adoptive transfer of Tfh cells significantly exacerbated the severity of CIA; however, the effect of Tfh cells on exacerbating the CIA process was significantly diminished after inhibiting sEVs secretion. Moreover, the levels of plasma Tfh-like-sEVs and CD40L expression on Tfh-like-sEVs in RA patients were significantly higher than those in healthy subjects. In summary, Tfh cell-derived sEVs can enhance the B-cell response, and exacerbate the procession of autoimmune arthritis.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103235"},"PeriodicalIF":12.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140818344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired LAIR-1-mediated immune control due to collagen degradation in fibrosis","authors":"Tiago Carvalheiro ,&nbsp;Wioleta Marut ,&nbsp;M. Inês Pascoal Ramos ,&nbsp;Samuel García ,&nbsp;Devan Fleury ,&nbsp;Alsya J. Affandi ,&nbsp;Aniek S. Meijers ,&nbsp;Barbara Giovannone ,&nbsp;Ralph G. Tieland ,&nbsp;Eline Elshof ,&nbsp;Andrea Ottria ,&nbsp;Marta Cossu ,&nbsp;Matthew L. Meizlish ,&nbsp;Tineke Veenendaal ,&nbsp;Meera Ramanujam ,&nbsp;Miguel E. Moreno-García ,&nbsp;Judith Klumperman ,&nbsp;Nalan Liv ,&nbsp;Timothy R.D.J. Radstake ,&nbsp;Linde Meyaard","doi":"10.1016/j.jaut.2024.103219","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103219","url":null,"abstract":"<div><p>Tissue repair is disturbed in fibrotic diseases like systemic sclerosis (SSc), where the deposition of large amounts of extracellular matrix components such as collagen interferes with organ function. LAIR-1 is an inhibitory collagen receptor highly expressed on tissue immune cells. We questioned whether in SSc, impaired LAIR-1-collagen interaction is contributing to the ongoing inflammation and fibrosis.</p><p>We found that SSc patients do not have an intrinsic defect in LAIR-1 expression or function. Instead, fibroblasts from healthy controls and SSc patients stimulated by soluble factors that drive inflammation and fibrosis in SSc deposit disorganized collagen products <em>in vitro</em>, which are dysfunctional LAIR-1 ligands. This is dependent of matrix metalloproteinases and platelet-derived growth factor receptor signaling.</p><p>In support of a non-redundant role of LAIR-1 in the control of fibrosis, we found that LAIR-1-deficient mice have increased skin fibrosis in response to repeated injury and in the bleomycin mouse model for SSc. Thus, LAIR-1 represents an essential control mechanism for tissue repair. In fibrotic disease, excessive collagen degradation may lead to a disturbed feedback loop. The presence of functional LAIR-1 in patients provides a therapeutic opportunity to reactivate this intrinsic negative feedback mechanism in fibrotic diseases.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103219"},"PeriodicalIF":12.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000532/pdfft?md5=b03d7b87059f52d6e15cd85cd86ad321&pid=1-s2.0-S0896841124000532-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140816068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}