Journal of autoimmunity最新文献

{"title":"Pin1 maintains the effector program of pathogenic Th17 cells in autoimmune neuroinflammation","authors":"Guangyue Fan ,&nbsp;Guangliang Li ,&nbsp;Long Li ,&nbsp;Yurong Da","doi":"10.1016/j.jaut.2024.103262","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103262","url":null,"abstract":"<div><p>Th17 cells mediated immune response is the basis of a variety of autoimmune diseases, including multiple sclerosis and its mouse model of immune aspects, experimental autoimmune encephalomyelitis (EAE). The gene network that drives both the development of Th17 and the expression of its effector program is dependent on the transcription factor RORγt. In this report, we showed that Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (Pin1) formed a complex with RORγt, and enhanced its transactivation activity, thus sustained the expression of the effector genes as well as RORγt in the EAE-pathogenic Th17 cells. We first found out that <em>PIN1</em> was highly expressed in the samples from patients of multiple sclerosis, and the expression of Pin1 by the infiltrating lymphocytes in the central nerve system of EAE mice was elevated as well. An array of experiments with transgenic mouse models, cellular and molecular assays was included in the study to elucidate the role of Pin1 in the pathology of EAE. It turned out that Pin1 promoted the activation and maintained the effector program of EAE-pathogenic Th17 cells in the inflammation foci, but had little effect on the priming of Th17 cells in the draining lymph nodes. Mechanistically, Pin1 stabilized the phosphorylation of STAT3 induced by proinflammatory stimuli, and interacted with STAT3 in the nucleus of Th17 cells, which resulted in the increased expression of <em>Rorc</em>. Moreover, Pin1 formed a complex with RORγt, and enhanced the transactivation of RORγt to the +11 kb enhancer of <em>Rorc</em>, which enforced and maintained the expression of both <em>Rorc</em> and the effector program of pathogenic Th17 cells in EAE. Finally, the inhibition of Pin1, by genetic knockdown or by small molecule inhibitor, deceased the population of Th17 cells and the neuroinflammation, and alleviated the symptoms of EAE. These findings suggest that Pin1 is a potential therapeutic target for MS and other autoimmune inflammatory diseases.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"147 ","pages":"Article 103262"},"PeriodicalIF":12.8,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141243015","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":"Adding salt to foods and risk of psoriasis: A prospective cohort study","authors":"Guowei Zhou ,&nbsp;Lu Gan ,&nbsp;Bin Zhao ,&nbsp;Fang Fang ,&nbsp;Hong Liu ,&nbsp;Xiang Chen ,&nbsp;Jiaqi Huang","doi":"10.1016/j.jaut.2024.103259","DOIUrl":"10.1016/j.jaut.2024.103259","url":null,"abstract":"<div><h3>Background</h3><p>High salt intake may play a critical role in the etiology of psoriasis. Yet, evidence on the association of high salt intake with risk of psoriasis is limited.</p></div><div><h3>Objective</h3><p>To estimate the association between frequency of adding salt to foods and risk of psoriasis.</p></div><div><h3>Methods</h3><p>We conducted a prospective cohort study of 433,788 participants from the UK Biobank. Hazard ratios (HRs) and their 95 % confidence intervals (CIs) for risk of psoriasis in relation to frequency of adding salt to foods were estimated using multivariable Cox proportional hazards models. We further evaluated the joint association of adding salt to foods and genetic susceptibility with risk of psoriasis. We conducted a mediation analysis to assess how much of the effect of adding salt to foods on risk of psoriasis was mediated through several selected mediators.</p></div><div><h3>Results</h3><p>During a median of 14.0 years of follow-up, 4279 incident cases of psoriasis were identified. In the multivariable-adjusted model, a higher frequency of adding salt to foods was significantly associated with an increased risk of psoriasis (“always” versus “never/rarely” adding salt to foods, HR = 1.25, 95 % CI: 1.10, 1.41). The observed positive association was generally similar across subgroups. In the joint association analysis, we observed that participants with a high genetic risk (above the second tertile) and the highest frequency of adding salt to foods experienced 149 % higher risk of psoriasis, when compared with participants with a low genetic risk (below the first tertile) and the lowest frequency of adding salt to foods (HR = 2.49, 95 % CI: 2.05, 3.02). Mediation analysis revealed that 1.8 %–3.2 % of the positive association between frequency of adding salt and risk of psoriasis was statistically significantly mediated by obesity and inflammatory biomarkers such as C-reactive protein and systemic immune-inflammation index (all P values &lt; 0.004).</p></div><div><h3>Conclusions</h3><p>Our study demonstrated a positive association between frequency of adding salt to foods and risk of psoriasis. The positive association was independent of multiple other risk factors, and may be partially mediated through obesity and inflammation.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"147 ","pages":"Article 103259"},"PeriodicalIF":12.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186528","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":"Cannabinoid receptor 2 selective agonist alleviates systemic sclerosis by inhibiting Th2 differentiation through JAK/SOCS3 signaling","authors":"Na Tian ,&nbsp;Hao Cheng ,&nbsp;Yu Du ,&nbsp;Xiaoxia Wang ,&nbsp;Yi Lei ,&nbsp;Xinnan Liu ,&nbsp;Miao Chen ,&nbsp;Zhan Xu ,&nbsp;Lingbiao Wang ,&nbsp;Hanlin Yin ,&nbsp;Rong Fu ,&nbsp;Dan Li ,&nbsp;Penghui Zhou ,&nbsp;Liangjing Lu ,&nbsp;Zhinan Yin ,&nbsp;Sheng-Ming Dai ,&nbsp;Bin Li","doi":"10.1016/j.jaut.2024.103233","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103233","url":null,"abstract":"<div><p>Systemic sclerosis (SSc) poses a significant challenge in autoimmunology, characterized by the development of debilitating fibrosis of skin and internal organs. The pivotal role of dysregulated T cells, notably the skewed polarization toward Th2 cells, has been implicated in the vascular damage and progressive fibrosis observed in SSc. In this study, we explored the underlying mechanisms by which cannabinoid receptor 2 (CB2) highly selective agonist HU-308 restores the imbalance of T cells to alleviate SSc. Using a bleomycin-induced SSc (BLM-SSc) mouse model, we demonstrated that HU-308 effectively attenuates skin and lung fibrosis by specifically activating CB2 on CD4⁺ T cells to inhibit the polarization of Th2 cells in BLM-SSc mice, which was validated by Cnr2-specific-deficient mice. Different from classical signaling downstream of G protein-coupled receptors (GPCRs), HU-308 facilitates the expression of SOCS3 protein and subsequently impedes the IL2/STAT5 signaling pathway during Th2 differentiation. The deficiency of SOCS3 partially mitigated the impact of HU-308. Analysis of a cohort comprising 80 SSc patients and 82 healthy controls revealed an abnormal elevation in the Th2/Th1 ratio in SSc patients. The proportion of Th2 cells showed a significant positive correlation with mRSS score and positivity of anti-Scl-70. Administration of HU-308 to PBMCs and peripheral CD4⁺ T cells from SSc patients led to the upregulation of SOCS3, which effectively suppressed the aberrantly activated STAT5 signaling pathway and the proportion of CD4⁺IL4⁺ T cells. In conclusion, our findings unveil a novel mechanism by which the CB2 agonist HU-308 ameliorates fibrosis in SSc by targeting and reducing Th2 responses. These insights provide a foundation for future therapeutic approaches in SSc by modulating Th2 responses.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"147 ","pages":"Article 103233"},"PeriodicalIF":12.8,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097785","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":"JAK inhibitors in refractory juvenile rheumatic diseases: Efficacy, tolerance and type-I interferon profiling, a single center retrospective study","authors":"Marie Solignac ,&nbsp;Natalia Cabrera ,&nbsp;Marine Fouillet-Desjonqueres ,&nbsp;Agnes Duquesne ,&nbsp;Audrey Laurent ,&nbsp;Anne-Perrine Foray ,&nbsp;Sebastien Viel ,&nbsp;Franck Zekre ,&nbsp;Alexandre Belot","doi":"10.1016/j.jaut.2024.103248","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103248","url":null,"abstract":"<div><h3>Objectives</h3><p><em>–</em> Janus Kinase inhibitors (JAKi) are a new class of drugs available for pediatric rheumatic diseases.</p><p>This study aimed to describe the safety and effectiveness of JAKi in these diseases, with a focus on longitudinal interferon-stimulated genes (ISG) assessment.</p></div><div><h3>Methods</h3><p><em>–</em> We present a single-center retrospective study of children with refractory pediatric rheumatic diseases including connective tissue diseases, monogenic type I interferonopathies or juvenile idiopathic arthritis, receiving JAKi. According to physicians’ assessment, treatment effectiveness was classified at 12 months as a complete response in the total absence of disease activity, partial response in case of significant (&gt;50%) but incomplete improvement or no response in the case of non-response or improvement of less than 50% of the clinical and biological parameters. ISG were monitored longitudinally using Nanostring technology.</p></div><div><h3>Results</h3><p><em>-</em> 22 children were retrospectively included in this study, treated either by baricitinib or ruxolitinib. Complete response was achieved at 12 months in 9/22 (41%) patients. 6/22 (27%) patients were non-responders and treatment had been discontinued in five of them. Within the interferon (IFN)-related diseases group, ISG-score was significantly reduced 12 months after JAKi onset (p = 0.0068). At 12 months, daily glucocorticoid doses had been reduced with a median dose of 0.16 mg/kg/day (IQR 0.11; 0.33) (p = 0.0425). 7/22 (32%) patients had experienced side effects, infections being the most common. Increase of the body mass index was also recorded in children in the first 6 months of treatment.</p></div><div><h3>Conclusion</h3><p><em>–</em> JAKi represent a promising treatment of immune-mediated pediatric diseases, enabling to decrease type-I IFN transcriptomic signature in responding patients, especially in the context of juvenile dermatomyositis. JAKi represent steroid-sparing drugs but they induce metabolic changes linked to weight gain, posing a concern in the treatment of young patients and teenagers. More data are required to define the efficacy and safety of JAKi in the management of refractory pediatric rheumatic diseases.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"147 ","pages":"Article 103248"},"PeriodicalIF":12.8,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000829/pdfft?md5=e99a7e46acc50951a7d761dfe499727f&pid=1-s2.0-S0896841124000829-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141095543","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":"Circulating extracellular vesicles and small non-coding RNAs cargo in idiopathic inflammatory myopathies reveal differences across myositis subsets","authors":"Chiara Franco ,&nbsp;Alessandra Giannella ,&nbsp;Michela Gasparotto ,&nbsp;Elisabetta Zanatta ,&nbsp;Anna Ghirardello ,&nbsp;Federico Pettorossi ,&nbsp;Zahrà Rahmè ,&nbsp;Roberto Depascale ,&nbsp;Davide Ragno ,&nbsp;Gioele Bevilacqua ,&nbsp;Elisa Bellis ,&nbsp;Luca Iaccarino ,&nbsp;Andrea Doria ,&nbsp;Giulio Ceolotto ,&nbsp;Mariele Gatto","doi":"10.1016/j.jaut.2024.103255","DOIUrl":"10.1016/j.jaut.2024.103255","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the epigenetic footprint of idiopathic inflammatory myopathies (IIM) through characterization of circulating extracellular vesicles (EVs) and the expression of EV-derived small non-coding RNAs (sncRNAs).</p></div><div><h3>Methods</h3><p>In this cross-sectional study, EVs were isolated by size-exclusion chromatography from plasma of patients with IIM and age- and sex-matched healthy donors (HD). EV-derived sncRNAs were sequenced and quantified using Next-Generation Sequencing (NGS). Following quality control and normalization, filtered count reads were used for differential microRNA (miRNA) and piwi-interacting RNA (piRNA) expression analyses. Putative gene targets enriched for pathways implicated in IIM were analyzed. Patients’ clinical and laboratory characteristics at the time of sampling were recorded.</p></div><div><h3>Results</h3><p>Forty-seven IIM patients and 45 HD were enrolled. MiR-486-5p (p &lt; 0.01), miR-122-5p, miR-192-5p, and miR-32-5p were significantly upregulated (p &lt; 0.05 for all), while miR-142-3p (p &lt; 0.001), miR-141-3p (p &lt; 0.01), let-7a-5p (p &lt; 0.05) and miR-3613-5p (p &lt; 0.05) downregulated in EVs from IIM patients versus HD. MiR-486-5p was associated with raised muscle enzymes levels. Several target genes of up/downregulated miRNAs in IIM participate in inflammation, necroptosis, interferon and immune signaling. Six piRNAs were significantly dysregulated in IIM EVs versus HD (p &lt; 0.05). Within IIM, miR-335-5p was selectively upregulated and miR-27a-5p downregulated in dermatomyositis (n = 21, p &lt; 0.01). Finally, plasma EV levels were significantly increased in cancer-associated myositis (CAM, n = 12) versus non-CAM IIM (n = 35, p = 0.02) and HD (p &lt; 0.01). EVs cargo in CAM was significantly enriched of let-7f-5p and depleted of miR-143-3p.</p></div><div><h3>Conclusion</h3><p>Through an unbiased screening of EV-derived sncRNAs, we characterize miRNAs and piRNAs in the EVs cargo as potential biomarkers and modifiers of diverse IIM phenotypes.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"147 ","pages":"Article 103255"},"PeriodicalIF":12.8,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000891/pdfft?md5=7d65d3e746c769b6a08f94058c8de3fe&pid=1-s2.0-S0896841124000891-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093461","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":"Autoreactivity to self-antigens LL37 and ADAMTSL5 influences the clinical response to risankizumab in psoriatic patients","authors":"Rebecca Favaro ,&nbsp;Paola Facheris ,&nbsp;Alessandra Formai ,&nbsp;Luigi Gargiulo ,&nbsp;Luciano Ibba ,&nbsp;Giovanni Fiorillo ,&nbsp;Roberta Valeria Latorre ,&nbsp;Jessica Avagliano ,&nbsp;Alessandra Narcisi ,&nbsp;Giampiero Girolomoni ,&nbsp;Santo Raffaele Mercuri ,&nbsp;Antonio Costanzo","doi":"10.1016/j.jaut.2024.103244","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103244","url":null,"abstract":"<div><p>The autoantigens LL37 and ADAMTSL5 contribute to induce pathogenetic T-cells responses in a subset of psoriatic patients. Whether the presence of LL37-and/or ADAMTS5-reactive T-cells influences the clinical response to treatment is still unknown.</p><p>The aim of the study is to evaluate the clinical responses to the anti-IL-23 risankizumab in LL37 and/or ADAMTSL5-reactive patients in comparison with non-reactive ones and to assess whether genetics (HLA-Cw06.02) or BMI influences the response to treatment. Patients were screened at baseline for the presence of circulating LL37 or/and ADAMTSL5-reactive T-cells and were treated as per protocol with risankizumab. Effectiveness data (PASI scores) were collected at weeks 4, 16, 28, 40 and 52. Data were also analyzed based on HLA-Cw06.02 status and BMI.</p><p>The overall response to treatment of patients with autoreactivity to LL37 or ADAMTSL5 did not differ compared to the non-reactive cohort as measured as PASI75/90/100 at different time points; however, subjects that had autoreactive T-cells to both LL37 and ADAMTS5 demonstrated suboptimal response to treatment starting at week16. HLA-Cw06:02⁺ patients demonstrated faster response to risankizumab at week 4 compared to HLA-Cw06:02^-. Additionally, the response to treatment was influenced by the BMI with slower responses seen in overweight and obese patients at week 4 and week16.</p><p>In conclusion, while the presence of either LL37-and ADAMTS5-reactive circulating T-cells do not influence the clinical response to risankizumab, the presence of the double reactivity to both LL37 and ADAMTS5 decreases the clinical responses. Moreover, we evidenced that HLA-Cw06⁺ respond faster to IL-23 inhibition and that BMI, associated to autoreactivity, can influence the speed in response.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"147 ","pages":"Article 103244"},"PeriodicalIF":12.8,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141095542","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":"Polymyalgia rheumatica shows metabolomic alterations that are further altered by glucocorticoid treatment: Identification of metabolic correlates of fatigue","authors":"Julia E. Manning ,&nbsp;Emma Harris ,&nbsp;Hannah Mathieson ,&nbsp;Louise Sorensen ,&nbsp;Raashid Luqmani ,&nbsp;Helen M. McGettrick ,&nbsp;Ann W. Morgan ,&nbsp;Stephen P. Young ,&nbsp;Sarah L. Mackie","doi":"10.1016/j.jaut.2024.103260","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103260","url":null,"abstract":"<div><h3>Objective</h3><p>In polymyalgia rheumatica (PMR), glucocorticoids (GCs) relieve pain and stiffness, but fatigue may persist. We aimed to explore the effect of disease, GCs and PMR symptoms in the metabolite signatures of peripheral blood from patients with PMR or the related disease, giant cell arteritis (GCA).</p></div><div><h3>Methods</h3><p>Nuclear magnetic resonance spectroscopy was performed on serum from 40 patients with untreated PMR, 84 with new-onset confirmed GCA, and 53 with suspected GCA who later were clinically confirmed non-GCA, and 39 age-matched controls. Further samples from PMR patients were taken one and six months into glucocorticoid therapy to explore relationship of metabolites to persistent fatigue. 100 metabolites were identified using Chenomx and statistical analysis performed in SIMCA-P to examine the relationship between metabolic profiles and, disease, GC treatment or symptoms.</p></div><div><h3>Results</h3><p>The metabolite signature of patients with PMR and GCA differed from that of age-matched non-inflammatory controls (R² &gt; 0.7). There was a smaller separation between patients with clinically confirmed GCA and those with suspected GCA who later were clinically confirmed non-GCA (R² = 0.135). In PMR, metabolite signatures were further altered with glucocorticoid treatment (R² = 0.42) but did not return to that seen in controls. Metabolites correlated with CRP, pain, stiffness, and fatigue (R² ≥ 0.39). CRP, pain, and stiffness declined with treatment and were associated with 3-hydroxybutyrate and acetoacetate, but fatigue did not. Metabolites differentiated patients with high and low fatigue both before and after treatment (R² &gt; 0.9). Low serum glutamine was predictive of high fatigue at both time points (0.79-fold change).</p></div><div><h3>Conclusion</h3><p>PMR and GCA alter the metabolite signature. In PMR, this is further altered by glucocorticoid therapy. Treatment-induced metabolite changes were linked to measures of inflammation (CRP, pain and stiffness), but not to fatigue. Furthermore, metabolite signatures distinguished patients with high or low fatigue.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"147 ","pages":"Article 103260"},"PeriodicalIF":12.8,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000945/pdfft?md5=18a19bdc225b56172a0692cca9cebabc&pid=1-s2.0-S0896841124000945-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097786","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":"Immune interplay from circulation to local lesion in pemphigus pathogenesis","authors":"Li Lei,&nbsp;SuYing Feng","doi":"10.1016/j.jaut.2024.103261","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103261","url":null,"abstract":"<div><p>Pemphigus, a potentially lethal autoimmune skin disease, is mediated by desmoglein-specific antibodies, manifesting cutaneous and mucosal blisters and erosions. The interaction between multiple immune counterparts contributes to the progress of pemphigus. Currently, the emergence of bioinformatic analysis enables investigators to gain a global picture of the pemphigus immune network, based on the exhaustive pedigree annotation of multiple subsets. T helper subsets dominate the landscape as mentioned previously, and innate immune cells have been involved as well. Of particular interests is which phenotype of T cells orchestrates the autoimmune process and chronic inflammation in a certain condition. In this review, the circulatory and peripheral immune cells and cytokine components constituting the immune microenvironment are separately discussed to provide a perspective on pemphigus pathogenesis, with particular reference to insights provided by the bioinformation technique.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"147 ","pages":"Article 103261"},"PeriodicalIF":12.8,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097788","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":"Diverse immunological dysregulation, chronic inflammation, and impaired erythropoiesis in long COVID patients with chronic fatigue syndrome","authors":"Suguru Saito ,&nbsp;Shima Shahbaz ,&nbsp;Mohammed Osman ,&nbsp;Desiree Redmond ,&nbsp;Najmeh Bozorgmehr ,&nbsp;Rhonda J. Rosychuk ,&nbsp;Grace Lam ,&nbsp;Wendy Sligl ,&nbsp;Jan Willem Cohen Tervaert ,&nbsp;Shokrollah Elahi","doi":"10.1016/j.jaut.2024.103267","DOIUrl":"https://doi.org/10.1016/j.jaut.2024.103267","url":null,"abstract":"<div><p>A substantial number of patients recovering from acute SARS-CoV-2 infection present serious lingering symptoms, often referred to as long COVID (LC). However, a subset of these patients exhibits the most debilitating symptoms characterized by ongoing myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). We specifically identified and studied ME/CFS patients from two independent LC cohorts, at least 12 months post the onset of acute disease, and compared them to the recovered group (R). ME/CFS patients had relatively increased neutrophils and monocytes but reduced lymphocytes. Selective T cell exhaustion with reduced naïve but increased terminal effector T cells was observed in these patients. LC was associated with elevated levels of plasma pro-inflammatory cytokines, chemokines, Galectin-9 (Gal-9), and artemin (ARTN). A defined threshold of Gal-9 and ARTN concentrations had a strong association with LC. The expansion of immunosuppressive CD71⁺ erythroid cells (CECs) was noted. These cells may modulate the immune response and contribute to increased ARTN concentration, which correlated with pain and cognitive impairment. Serology revealed an elevation in a variety of autoantibodies in LC. Intriguingly, we found that the frequency of 2B4⁺CD160⁺ and TIM3⁺CD160⁺ CD8⁺ T cells completely separated LC patients from the R group. Our further analyses using a multiple regression model revealed that the elevated frequency/levels of CD4 terminal effector, ARTN, CEC, Gal-9, CD8 terminal effector, and MCP1 but lower frequency/levels of TGF-β and MAIT cells can distinguish LC from the R group. Our findings provide a new paradigm in the pathogenesis of ME/CFS to identify strategies for its prevention and treatment.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"147 ","pages":"Article 103267"},"PeriodicalIF":12.8,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S089684112400101X/pdfft?md5=5edd7a694b8a1daa0b356c913523c59e&pid=1-s2.0-S089684112400101X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097787","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 autoimmune response induced by α-synuclein peptides drives neuronal cell death and glial cell activation","authors":"Yong-ho Choe ,&nbsp;Min Gi Jo ,&nbsp;Bo Gyu Kim ,&nbsp;Sangwon Lee ,&nbsp;Bina Lee ,&nbsp;Seon-Hee Kim ,&nbsp;Hyemin Seong ,&nbsp;Woong-Sun Yoo ,&nbsp;Minkyeong Kim ,&nbsp;Dong-Kun Lee ,&nbsp;Seong Jae Kim ,&nbsp;Seung Pil Yun ,&nbsp;Mingyo Kim","doi":"10.1016/j.jaut.2024.103256","DOIUrl":"10.1016/j.jaut.2024.103256","url":null,"abstract":"<div><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses. However, it is unclear whether the α-Syn-mediated autoimmune response occurs and whether it is related to neuronal cell death and glial cell activation. In this study, we investigated the autoimmune T-cell response induced by α-Syn peptides and evaluated the neurotoxic effect of the α-Syn peptide-mediated autoimmune response. The immunization of mice with α-Syn peptides resulted in enhanced autoimmune responses, such as the peptide recall response, polarization toward Th1/Th17 cells, and regulatory T cell imbalance. Furthermore, the α-Syn autoimmune response led to the death of primary neurons cocultured with splenocytes. Treatment with conditioned media from α-Syn peptide-immunized splenocytes induced microglia and toxic A1-type astrocyte activation. Taken together, our results provide evidence of the potential role of the α-Syn-initiated autoimmune response and its contribution to neuronal cell death and glial cell activation.</p></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"147 ","pages":"Article 103256"},"PeriodicalIF":12.8,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0896841124000908/pdfft?md5=38790f3eed14e2de19cbf8895f68c974&pid=1-s2.0-S0896841124000908-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093506","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}