Journal of autoimmunity最新文献

{"title":"Circulating immune profile in granulomatosis with polyangiitis reveals distinct patterns related to disease activity","authors":"C.G. Bonasia ,&nbsp;N. Inrueangsri ,&nbsp;T. Bijma ,&nbsp;K.P. Mennega ,&nbsp;R. Wilbrink ,&nbsp;S. Arends ,&nbsp;W.H. Abdulahad ,&nbsp;N.A. Bos ,&nbsp;A. Rutgers ,&nbsp;P. Heeringa","doi":"10.1016/j.jaut.2024.103236","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103236","url":null,"abstract":"<div><p>Granulomatosis with polyangiitis (GPA) is an autoimmune disorder characterized by recurrent relapses that can cause severe tissue damage and life-threatening organ dysfunction. Multiple immune cells and cytokines/chemokines are involved in the different stages of the disease. Immune profiling of patients may be useful for tracking disease activity, however, reliable immune signatures for GPA activity are lacking. In this study, we examined circulating immune profiles in GPA patients during active and remission disease states to identify potential immune patterns associated with disease activity.</p><p>The distribution and phenotypic characteristics of major circulating immune cells, and the profiles of circulating cytokines/chemokines, were studied on cryopreserved peripheral blood mononuclear cells from GPA patients (active, n = 20; remission, n = 20) and healthy controls (n = 20) leveraging a 40-color optimized multicolor immunofluorescence panel (OMIP-69) and in serum using a 46-plex Luminex multiplex assay, respectively.</p><p>Deep phenotyping uncovered a distinct composition of major circulating immune cells in active GPA and GPA in remission, with the most significant findings emerging within the monocyte compartment. Our detailed analysis revealed circulating monocyte diversity beyond the conventional monocyte subsets. We identified eight classical monocyte populations, two intermediate monocyte populations, and one non-classical monocyte population. Notably, active GPA had a higher frequency of CD45RA⁺CCR5⁺CCR6⁻CCR7^+/lowCD127⁻HLA-DR⁺CD2⁻ classical monocytes and a lower frequency of CD45RA⁻CCR5^-/lowCCR6⁻CCR7⁻CD127⁻HLA-DR⁺CD2^+/− classical monocytes, which both strongly correlated with disease activity. Furthermore, serum levels of CXCL1, CXCL2, and CCL20, all linked to monocyte biology, were elevated in active GPA and correlated strongly with disease activity.</p><p>These findings shed light on the circulating immune profile of GPA and may lead to immune signature profiles for assessing disease activity. Monocytes in particular may be studied further as potential markers for monitoring GPA.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103236"},"PeriodicalIF":12.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000702/pdfft?md5=368a07c2c368ff60d6baca8f67b25e79&pid=1-s2.0-S0896841124000702-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140816067","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":"Single cell transcriptomics of cerebrospinal fluid cells from patients with recent-onset narcolepsy","authors":"Alina Huth ,&nbsp;Ikram Ayoub ,&nbsp;Lucie Barateau ,&nbsp;Lisa Ann Gerdes ,&nbsp;Dany Severac ,&nbsp;Stefan Krebs ,&nbsp;Helmut Blum ,&nbsp;Hayrettin Tumani ,&nbsp;Jürgen Haas ,&nbsp;Brigitte Wildemann ,&nbsp;Tania Kümpfel ,&nbsp;Eduardo Beltrán ,&nbsp;Roland S. Liblau ,&nbsp;Yves Dauvilliers ,&nbsp;Klaus Dornmair","doi":"10.1016/j.jaut.2024.103234","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103234","url":null,"abstract":"<div><p>Narcolepsy is a rare cause of hypersomnolence and may be associated or not with cataplexy, i.e. sudden muscle weakness. These forms are designated narcolepsy-type 1 (NT1) and -type 2 (NT2), respectively. Notable characteristics of narcolepsy are that most patients carry the <em>HLA-DQB1*06:02</em> allele and NT1-patients have strongly decreased levels of hypocretin-1 (synonym orexin-A) in the cerebrospinal fluid (CSF). The pathogenesis of narcolepsy is still not completely understood but the strong HLA-bias and increased frequencies of CD4⁺ T cells reactive to hypocretin in the peripheral blood suggest autoimmune processes in the hypothalamus. Here we analyzed the transcriptomes of CSF-cells from twelve NT1 and two NT2 patients by single cell RNAseq (scRNAseq). As controls, we used CSF cells from patients with multiple sclerosis, radiologically isolated syndrome, and idiopathic intracranial hypertension. From 27,255 CSF cells, we identified 20 clusters of different cell types and found significant differences in three CD4⁺ T cell and one monocyte clusters between narcolepsy and multiple sclerosis patients. Over 1000 genes were differentially regulated between patients with NT1 and other diseases. Surprisingly, the most strongly upregulated genes in narcolepsy patients as compared to controls were coding for the genome-encoded MTRNR2L12 and MTRNR2L8 peptides, which are homologous to the mitochondria-encoded HUMANIN peptide that is known playing a role in other neurological diseases including Alzheimer's disease.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103234"},"PeriodicalIF":12.8,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000684/pdfft?md5=a234b99ad1683e34e3ecfabab6691d2c&pid=1-s2.0-S0896841124000684-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140645770","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":"Impaired IL-6-induced JAK-STAT signaling in CD4+ T cells associates with longer treatment duration in giant cell arteritis","authors":"Idil Esen ,&nbsp;Maria Sandovici ,&nbsp;Peter Heeringa ,&nbsp;Annemieke M.H. Boots ,&nbsp;Elisabeth Brouwer ,&nbsp;Yannick van Sleen ,&nbsp;Wayel Abdulahad","doi":"10.1016/j.jaut.2024.103215","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103215","url":null,"abstract":"<div><h3>Introduction</h3><p>The IL-12-IFNγ-Th1 and the IL-6-IL-23-Th17 axes are considered the dominant pathogenic pathways in Giant Cell Arteritis (GCA). Both pathways signal via activation of the downstream JAK/STAT proteins. We hypothesized that phosphorylated STAT (pSTAT) signatures in circulating immune cells may aid to stratify GCA-patients for personalized treatment.</p></div><div><h3>Methods</h3><p>To investigate pSTAT expression, PBMCs from treatment-naive GCA-patients (n = 18), infection controls (INF, n = 11) and age-matched healthy controls (HC, n = 15) were stimulated in vitro with IL-6, IL-2, IL-10, IFN-γ, M-CSF or GM-CSF, and stained with CD3, CD4, CD19, CD45RO, pSTAT1, pSTAT3, pSTAT5 antibodies, and analyzed by flow cytometry. Serum IL-6, sIL-6-receptor and gp130 were measured by Luminex. The change in percentages of pSTAT3+CD4+T-cells was evaluated at diagnosis and at 3 months and 1-year of follow-up. Kaplan-Meier analyses was used to asses prognostic accuracy.</p></div><div><h3>Results</h3><p>Analysis of IL-6 stimulated immune cell subsets revealed a significant decrease in percentages of pSTAT3+CD4+T-cells of GCA-patients and INF-controls compared to HCs. Following patient stratification according to high (median&gt;1.5 pg/mL) and low (median&lt;1.5 pg/mL) IL-6 levels, we observed a reduction in the pSTAT3 response in GCA-patients with high serum IL-6. Percentages of pSTAT3+CD4+T-cells in patients with high serum IL-6 levels at diagnosis normalized after glucocorticoid (GC) treatment. Importantly, we found that patients with low percentages of pSTAT3+CD4+T-cells at baseline require longer GC-treatment.</p></div><div><h3>Conclusion</h3><p>Overall, in GCA, the percentages of in vitro IL-6-induced pSTAT3+CD4+T-cells likely reflect prior in vivo exposure to high IL-6 and may serve as a prognostic marker for GC-treatment duration and may assist improving personalized treatment options in the future.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103215"},"PeriodicalIF":12.8,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000490/pdfft?md5=d4ac50d9ec4c0d83df4ed95032930878&pid=1-s2.0-S0896841124000490-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632796","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":"Blockade of neutrophil extracellular trap components ameliorates cholestatic liver disease in Mdr2 (Abcb4) knockout mice","authors":"Edith Hintermann ,&nbsp;Camilla Tondello ,&nbsp;Sina Fuchs ,&nbsp;Monika Bayer ,&nbsp;Josef M. Pfeilschifter ,&nbsp;Richard Taubert ,&nbsp;Martin Mollenhauer ,&nbsp;Roland P.J. Oude Elferink ,&nbsp;Michael P. Manns ,&nbsp;Urs Christen","doi":"10.1016/j.jaut.2024.103229","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103229","url":null,"abstract":"<div><p>Primary sclerosing cholangitis (PSC) is an (auto)immune-mediated cholestatic liver disease with a yet unclear etiology. Increasing evidence points to an involvement of neutrophils in chronic liver inflammation and cirrhosis but also liver repair. Here, we investigate the role of the neutrophil extracellular trap (NET) component myeloperoxidase (MPO) and the therapeutic potential of DNase I and of neutrophil elastase (NE) inhibitor GW311616A on disease outcome in the multidrug resistance 2 knockout (<em>Mdr2</em>^{<em>−/−</em>}) mouse, a PSC animal model. Initially, we observed the recruitment of MPO expressing cells and the formation of NETs in liver biopsies of PSC patients and in <em>Mdr2</em>^{<em>−/−</em>} livers. Furthermore, sera of <em>Mdr2</em>^{<em>−/−</em>} mice contained perinuclear anti-neutrophil cytoplasmic antibody (<em>p</em>-ANCA)-like reactivity similar to PSC patient sera. Also, hepatic NE activity was significantly higher in <em>Mdr2</em>^{<em>−/−</em>} mice than in wild type littermates. Flow cytometry analyses revealed that during disease development a highly active neutrophil subpopulation established specifically in the liver of <em>Mdr2</em>^{<em>−/−</em>} mice. However, absence of their MPO activity, as in MPO-deficient <em>Mdr2</em>^{<em>−/−</em>} mice, showed no effect on hepatobiliary disease severity. In contrast, clearance of extracellular DNA by DNase I reduced the frequency of liver-resident neutrophils, plasmacytoid dendritic cells (pDCs) and CD103⁺ conventional DCs and decreased cholangiocyte injury. Combination of DNase I with a pDC-depleting antibody was additionally hepatocyte-protective. Most importantly, GW311616A, an orally bioavailable inhibitor of human NE, attenuated hepatobiliary injury in a TNFα-dependent manner and damped hyperproliferation of biliary epithelial cells. Further, hepatic immigration and activity of CD11b⁺ DCs as well as the secretion of IFNγ by hepatic CD4 and CD8 T cells were reduced. Our findings delineate neutrophils as important participants in the immune cell crosstalk that drives cholestatic liver disease and identify NET components as potential therapeutic targets.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103229"},"PeriodicalIF":12.8,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000635/pdfft?md5=a71ac438b1d90d2c8740468ed07b8165&pid=1-s2.0-S0896841124000635-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632797","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":"PPARG-mediated autophagy activation alleviates inflammation in rheumatoid arthritis","authors":"Qishun Geng ,&nbsp;Jiahe Xu ,&nbsp;Xiaoxue Cao ,&nbsp;Zhaoran Wang ,&nbsp;Yi Jiao ,&nbsp;Wenya Diao ,&nbsp;Xing Wang ,&nbsp;Zihan Wang ,&nbsp;Mengxiao Zhang ,&nbsp;Lu Zhao ,&nbsp;Lei Yang ,&nbsp;Tingting Deng ,&nbsp;Bifa Fan ,&nbsp;Yuan Xu ,&nbsp;Lansi Jia ,&nbsp;Cheng Xiao","doi":"10.1016/j.jaut.2024.103214","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103214","url":null,"abstract":"<div><h3>Introduction</h3><p>Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease characterized by joint inflammation and bone damage, that not only restricts patient activity but also tends to be accompanied by a series of complications, seriously affecting patient prognosis. Peroxisome proliferator-activated receptor gamma (PPARG), a receptor that controls cellular metabolism, regulates the function of immune cells and stromal cells. Previous studies have shown that PPARG is closely related to the regulation of inflammation. However, the role of PPARG in regulating the pathological processes of RA is poorly understood.</p></div><div><h3>Materials and methods</h3><p>PPARG expression was examined in the synovial tissues and peripheral blood mononuclear cells (PBMCs) from RA patients and the paw of collagen-induced arthritis (CIA) model rats. Molecular biology experiments were designed to examine the effect of PPARG and cannabidiol (CBD) on RAW264.7 cells and CIA rats.</p></div><div><h3>Results</h3><p>The results reveal that PPARG accelerates reactive oxygen species (ROS) clearance by promoting autophagy, thereby inhibiting ROS-mediated macrophage polarization and NLRP3 inflammasome activation. Notably, CBD may be a promising candidate for understanding the mechanism by which PPARG regulates autophagy-mediated inflammation.</p></div><div><h3>Conclusions</h3><p>Taken together, these findings indicate that PPARG may have a role for distinguishing between RA patients and healthy control, and for distinguishing RA activity; moreover, PPARG could be a novel pharmacological target for alleviating RA through the mediation of autophagy. CBD can act as a PPARG agonist that alleviates the inflammatory progression of RA.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103214"},"PeriodicalIF":12.8,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140622361","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":"Multi-omics study reveals different pathogenesis of the generation of skin lesions in SLE and IDLE patients","authors":"Qianwen Li ,&nbsp;Chen Jia ,&nbsp;Wenjing Pan ,&nbsp;Hongmei Liu ,&nbsp;Congli Tang ,&nbsp;Daniel Weber ,&nbsp;Kaili Chen ,&nbsp;Hai Long ,&nbsp;Miranda L. Byrne-Steele ,&nbsp;Jian Han ,&nbsp;Nongyue He ,&nbsp;Rong Xiao ,&nbsp;Ming Zhao ,&nbsp;Nan Che ,&nbsp;Qing Guo ,&nbsp;Guangji Gui ,&nbsp;Shanshan Li ,&nbsp;Henan Si ,&nbsp;Shuping Guo ,&nbsp;Hongye Liu ,&nbsp;Qianjin Lu","doi":"10.1016/j.jaut.2024.103203","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103203","url":null,"abstract":"<div><p>Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, <em>HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01</em>, <em>HLA-C*03:02:02:01</em>, and <em>HLA-DQB1*02:01:01:01</em> positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103203"},"PeriodicalIF":12.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000374/pdfft?md5=f61dcb075a3289a5c3e133d22af9239b&pid=1-s2.0-S0896841124000374-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140622362","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":"UHRF1P contributes to IL-17A-mediated systemic lupus erythematosus via UHRF1-MAP4K3 axis","authors":"Huai-Chia Chuang ,&nbsp;Kuei-Yuan Lan ,&nbsp;Pu-Ming Hsu ,&nbsp;Ming-Han Chen ,&nbsp;Yi-Ming Chen ,&nbsp;Jeng-Hsien Yen ,&nbsp;Ben-Yang Liao ,&nbsp;Tse-Hua Tan","doi":"10.1016/j.jaut.2024.103221","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103221","url":null,"abstract":"<div><p>Inflammatory T cells contribute to the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Analysis of the T-cell transcriptomics data of two independent SLE patient cohorts by three machine learning models revealed the pseudogene UHRF1P as a novel SLE biomarker. The pseudogene-encoded UHRF1P protein was overexpressed in peripheral blood T cells of SLE patients. The UHRF1P protein lacks the amino-terminus of its parental UHRF1 protein, resulting in missing the proteasome-binding ubiquitin-like (Ubl) domain of UHRF1. T-cell-specific UHRF1P transgenic mice manifested the induction of IL-17A and autoimmune inflammation. Mechanistically, UHFR1P prevented UHRF1-induced Lys48-linked ubiquitination and degradation of MAP4K3 (GLK), which is a kinase known to induce IL-17A. Consistently, IL-17A induction and autoimmune phenotypes of UHRF1P transgenic mice were obliterated by MAP4K3 knockout. Collectively, UHRF1P overexpression in T cells inhibits the E3 ligase function of its parental UHRF1 and induces autoimmune diseases.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103221"},"PeriodicalIF":12.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000556/pdfft?md5=faee2a173b39c8f93773f61b5785bb42&pid=1-s2.0-S0896841124000556-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140622363","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 CD318/CD6 axis limits type 1 diabetes islet autoantigen-specific human T cell activation","authors":"Jeong-su Do ,&nbsp;David Arribas-Layton ,&nbsp;Jemily Juan ,&nbsp;Isaac Garcia ,&nbsp;Sindhu Saraswathy ,&nbsp;Meirigeng Qi ,&nbsp;Enrique Montero ,&nbsp;Helena Reijonen","doi":"10.1016/j.jaut.2024.103228","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103228","url":null,"abstract":"<div><p>CD6 is a glycoprotein expressed on CD4 and CD8 T cells involved in immunoregulation. CD318 has been identified as a CD6 ligand. The role of CD318 in T cell immunity is restricted as it has only been investigated in a few mice autoimmune models but not in human diseases. CD318 expression was thought to be limited to mesenchymal-epithelial cells and, therefore, contribute to CD6-mediated T cell activation in the CD318-expressing tissue rather than through interaction with antigen-presenting cells. Here, we report CD318 expression in a subpopulation of CD318⁺ myeloid dendritic (mDC), whereas the other peripheral blood populations were CD318 negative. However, CD318 can be induced by activation: a subset of monocytes treated with LPS and IFNγ and <em>in vitro</em> monocyte derived DCs were CD318⁺. We also showed that recombinant CD318 inhibited T cell function. Strikingly, CD318⁺ DCs suppressed the proliferation of autoreactive T cells specific for GAD65, a well-known targeted self-antigen in Type 1 Diabetes (T1D). Our study provides new insight into the role of the CD318/CD6 axis in the immunopathogenesis of inflammation, suggesting a novel immunoregulatory role of CD318 in T cell-mediated autoimmune diseases and identifying a potential novel immune checkpoint inhibitor as a target for intervention in T1D which is an unmet therapeutic need.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103228"},"PeriodicalIF":12.8,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140619449","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":"Anti-U1RNP antibodies are associated with a distinct clinical phenotype and a worse survival in patients with systemic sclerosis","authors":"Kevin Chevalier ,&nbsp;Guillaume Chassagnon ,&nbsp;Sarah Leonard-Louis ,&nbsp;Pascal Cohen ,&nbsp;Bertrand Dunogue ,&nbsp;Alexis Regent ,&nbsp;Benjamin Thoreau ,&nbsp;Luc Mouthon ,&nbsp;Benjamin Chaigne","doi":"10.1016/j.jaut.2024.103220","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103220","url":null,"abstract":"<div><h3>Objectives</h3><p>To clarify the impact of anti-U1RNP antibodies on the clinical features and prognosis of patients with SSc.</p></div><div><h3>Methods</h3><p>We conducted a monocentric case-control, retrospective, longitudinal study. For each patient with SSc and anti-U1RNP antibodies (SSc-RNP⁺), one patient with mixed connective tissue disease (MCTD) and 2 SSc patients without anti-U1RNP antibodies (SSc-RNP^-) were matched for age, sex, and date of inclusion.</p></div><div><h3>Results</h3><p>Sixty-four SSc-RNP⁺ patients were compared to 128 SSc-RNP^- and 64 MCTD patients. Compared to SSc-RNP^-, SSc-RNP⁺ patients were more often of Afro-Caribbean origin (31.3% <em>vs.</em> 11%, p &lt; 0.01), and more often had an overlap syndrome than SSc-RNP^- patients (53.1 % <em>vs.</em> 22.7%, p &lt; 0.0001), overlapping with Sjögren's syndrome (n = 23, 35.9%) and/or systemic lupus erythematosus (n = 19, 29.7%). SSc-RNP⁺ patients were distinctly different from MCTD patients but less often had joint involvement (p &lt; 0.01). SSc-RNP⁺ patients more frequently developed interstitial lung disease (ILD) (73.4% <em>vs.</em> 55.5% <em>vs.</em> 31.3%, p &lt; 0.05), pulmonary fibrosis (PF) (60.9% <em>vs</em>. 37.5% <em>vs</em>. 10.9%, p &lt; 0.0001), SSc associated myopathy (29.7% <em>vs.</em> 6.3% <em>vs.</em> 7.8%, p &lt; 0.0001), and kidney involvement (10.9% <em>vs.</em> 2.3% <em>vs.</em> 1.6%, p &lt; 0.05). Over a 200-month follow-up period, SSc-RNP⁺ patients had worse overall survival (p &lt; 0.05), worse survival without PF occurrence (p &lt; 0.01), ILD or PF progression (p &lt; 0.01 and p &lt; 0.0001).</p></div><div><h3>Conclusions</h3><p>In SSc patients, anti-U1RNP antibodies are associated with a higher incidence of overlap syndrome, a distinct clinical phenotype, and poorer survival compared to SSc-RNP^- and MCTD patients. Our study suggests that SSc-RNP⁺ patients should be separated from MCTD patients and may constitute an enriched population for progressive lung disease.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"146 ","pages":"Article 103220"},"PeriodicalIF":12.8,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140619421","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":"Interleukin-15 is a hair follicle immune privilege guardian","authors":"Takahiro Suzuki ,&nbsp;Jérémy Chéret ,&nbsp;Fernanda S. Dinelli ,&nbsp;Ali Rajabi-Estarabadi ,&nbsp;Aysun Akhundlu ,&nbsp;Dana-Lee Demetrius ,&nbsp;Jennifer Gherardini ,&nbsp;Aviad Keren ,&nbsp;Matthew Harries ,&nbsp;Jose Rodriguez-Feliz ,&nbsp;Gorana Epstein-Kuka ,&nbsp;Wendy Lee ,&nbsp;Talveen Purba ,&nbsp;Amos Gilhar ,&nbsp;Ralf Paus","doi":"10.1016/j.jaut.2024.103217","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103217","url":null,"abstract":"<div><p>The autoimmunity-promoting cytokine, Interleukin-15 (IL-15), is often claimed to be a key pathogenic cytokine in alopecia areata (AA). Yet, rhIL-15 promotes human hair follicle (HF) growth <em>ex vivo</em>. We have asked whether the expression of IL-15 and its receptor (IL-15R) isoforms is altered in human AA and how IL-15 impacts on human HF immune privilege (HF-IP) in the presence/absence of interferon-γ (IFNγ), the well-documented key AA-pathogenic cytokine, and on hair regrowth after experimental AA induction <em>in vivo</em>. Quantitative immunohistomorphometry showed the number of perifollicular IL-15⁺ T cells in AA skin biopsies to be significantly increased compared to healthy control skin, while IL-15, IL-15R-α, and IL-15R-γ protein expression within the hair bulb were significantly down-regulated in AA HFs. In organ-cultured human scalp HFs, rhIL-15 significantly reduced hair bulb expression of MICA, the key “danger” signal in AA pathogenesis, and increased production of the HF-IP guardian, α-MSH. Crucially, <em>ex vivo</em>, rhIL-15 prevented IFNγ-induced HF-IP collapse, restored a collapsed HF-IP by IL-15Rα-dependent signaling (as documented by IL-15Rα−silencing), and protected AA-preventive immunoinhibitory iNKT10 cells from IFNγ-induced apoptosis. rhIL-15 even promoted hair regrowth after experimental AA induction in human scalp skin xenotransplants on SCID/beige mice <em>in vivo</em>. Our data introduce IL-15 as a novel, functionally important HF-IP guardian whose signaling is constitutively defective in AA patients. Our data suggest that selective stimulation of intrafollicular IL-15Rα signaling could become a novel therapeutic approach in AA management, while blocking it pharmacologically may hinder both HF-IP restoration and hair re-growth and may thus make HFs more vulnerable to AA relapse.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"145 ","pages":"Article 103217"},"PeriodicalIF":12.8,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140347834","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}