Journal of Translational Autoimmunity最新文献

{"title":"Immune responses to infection and autoimmune diseases in the UK biobank","authors":"Choa Yun ,&nbsp;Dongwon Yoon ,&nbsp;Sun Young Jung ,&nbsp;Moonsuk Kim ,&nbsp;May A. Beydoun ,&nbsp;Lenore Launer ,&nbsp;Minkyo Song","doi":"10.1016/j.jtauto.2025.100315","DOIUrl":"10.1016/j.jtauto.2025.100315","url":null,"abstract":"<div><h3>Background</h3><div>Infections may trigger autoimmunity, but large-scale studies on antibodies to infections and their associations with autoimmune diseases are limited. We aim to better understand the etiologic role of infection.</div></div><div><h3>Methods</h3><div>We analyzed 9429 UK Biobank participants for 45 antibody responses to 20 pathogens. Association between seropositivity and autoimmune diseases was assessed with logistic regression for prevalence and Cox regression for incidence, applying Bonferroni correction. 49 autoimmune diseases were ascertained via International Classification of Diseases codes and self-reported diagnoses, of which 14 were analyzed.</div></div><div><h3>Results</h3><div>At baseline, 671 (7.1 %, 58 % female) had at least one autoimmune disease. In males, HSV-1 seropositivity was linked to lower odds of rheumatic fever/rheumatic heart disease (odds ratio 0.29 [95 % CI 0.12–0.68]), at Bonferroni significance. At nominal significance (p &lt; 0.05), eight associations were observed—positive: HHV-6B–type 1 diabetes, <em>H. pylori</em>–sarcoidosis, HPV-18–type 1 diabetes, JCV–psoriasis; inverse<strong>:</strong> <em>T. gondii</em>–celiac disease, <em>H. pylori</em>–Crohn’s disease, HSV-1–multiple sclerosis, HHV-7–rheumatoid arthritis. Of 8758 autoimmune disease-free individuals, 627 developed autoimmune diseases. In females, seropositivity to HPV-18 was associated with rheumatoid arthritis (hazard ratio 2.26 [95 % CI 1.34–3.82]), at Bonferroni significance. HRs for 3 nominal seropositivity/autoimmune disease associations (1 inverse, 2 positive) ranged from 0.42 [95 % CI 0.21–0.87] (HHV-6B/vasculitis) to 3.62 [95 % CI 1.29–10.12] (<em>C. trachomatis</em>/psoriasis) in both sexes.</div></div><div><h3>Conclusions</h3><div>This study examined cross-sectional and prospective associations between antibodies to infectious agents and autoimmune diseases. Inverse associations may suggest infections could train the immune system or reflect altered host immunity, while positive associations indicate potential autoimmune triggers. These findings enhance understanding of autoimmune disease etiology and provide a foundation for future mechanistic studies and hypothesis-driven research.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100315"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiological assessment of six major immune-mediated inflammatory diseases based on the Global Burden of Disease Study 2021: analyses of age-standardized incidence, prevalence, mortality, and disability-adjusted life years","authors":"Mengyu Huang ,&nbsp;Zhaoli Ma ,&nbsp;Xiu Luo ,&nbsp;Qian Ren","doi":"10.1016/j.jtauto.2025.100330","DOIUrl":"10.1016/j.jtauto.2025.100330","url":null,"abstract":"<div><h3>Objective</h3><div>Immune-mediated inflammatory diseases (IMIDs) are a group of chronic conditions characterized by dysregulated immune responses and tissue inflammation, posing a significant challenge to global health. However, comprehensive epidemiological analysis of the burden of these diseases remains limited. This study aimed to assess the trends in disease burden of six major IMIDs from 1990 to 2021 using the Global Burden of Disease (GBD) 2021 data, providing evidence for targeted prevention and control strategies.</div></div><div><h3>Methods</h3><div>Utilizing GBD 2021 data, we analyzed the epidemiological trends in age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized death rate (ASDR), and disability-adjusted life years (DALYs) for six IMIDs across global, 21 regions, 5 Socio-demographic Index (SDI) quintiles, and 204 countries and territories. Joinpoint regression analysis was employed to evaluate temporal trends and calculated the average annual percentage change (AAPC) and its 95% confidence interval (CI).</div></div><div><h3>Results</h3><div>From 1990 to 2021, global ASIR, ASPR, ASDR, and DALYs for asthma, atopic dermatitis (AD), and multiple sclerosis (MS) exhibited declining trends. In contrast, ASIR, ASPR, and DALYs for psoriasis (PsO) showed a comprehensive increasing trend. For inflammatory bowel disease (IBD) and rheumatoid arthritis (RA), ASIR increased significantly, while ASDR and DALYs decreased. Furthermore, significant regional heterogeneity in disease burden was observed: high-SDI regions typically demonstrated higher ASIR and ASPR but lower ASDR; conversely, low-SDI regions exhibited lower ASIR and ASPR alongside higher ASDR.</div></div><div><h3>Conclusion</h3><div>Despite significant spatiotemporal heterogeneity in the burden of the six IMIDs at global and regional levels, they collectively impose a substantial health burden worldwide. Consequently, future efforts require region-specific, differentiated public health interventions to address the ongoing challenge posed by IMIDs to global health systems.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100330"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rheumatoid factor and anti-citrullinated protein IgA antibodies in the diagnosis, prognosis and monitoring of patients with rheumatoid arthritis","authors":"Ulrike Steffen ,&nbsp;Daniela Sieghart ,&nbsp;Günter Steiner","doi":"10.1016/j.jtauto.2025.100332","DOIUrl":"10.1016/j.jtauto.2025.100332","url":null,"abstract":"<div><div>Over the past decades immunoglobulin A (IgA) antibodies have gained increasing attention for their diagnostic and prognostic significance in rheumatoid arthritis (RA), complementing the well-established roles of IgM rheumatoid factor (RF) and IgG anti-citrullinated protein antibodies (ACPA). IgA-RF and IgA-ACPA are found in a subset of RA patients and have been associated with more severe disease phenotypes, including increased joint erosion and extra-articular manifestations, especially cardiovascular disease and lung involvement. Moreover, concerning prediction of therapeutic responses IgA isotypes seem to have potential, as their presence has been shown to be associated with a blunted response to treatment with TNF inhibitors suggesting their usefulness for disease monitoring during follow-up once a diagnosis has been established. Although the diagnostic value of IgA autoantibodies in identifying seronegative RA cases is limited, their presence confirms a diagnosis of RA and may be helpful in the preclinical detection of individuals at risk for developing RA.</div><div>Increasing evidence suggests that IgA-RF and IgA-ACPA may contribute to disease pathogenesis. They can activate myeloid cells through engagement with the Fc alpha receptor I, leading to enhanced pro-inflammatory cytokine release, phagocytosis, and the formation of neutrophil extracellular traps that exacerbate tissue damage. Taken together, measuring IgA isotypes may be considered a valuable addition to the serological armamentarium for RA, with potential to improve early diagnosis, risk stratification, and personalized therapeutic approaches.</div><div>This review summarizes the current knowledge regarding the value of IgA-RF and IgA-ACPA as diagnostic and prognostic markers for RA. In addition, we discuss how the presence of IgA autoantibodies fits into the mucosal origin theory and describe their potential pathologic effects.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100332"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory T cell therapy for Sjögren's disease: From pathogenesis to targeted treatment","authors":"Zhi Feng Sherman Lim ,&nbsp;Alberta Y. Hoi ,&nbsp;Fabien B. Vincent ,&nbsp;Joshua D. Ooi ,&nbsp;Eric F. Morand ,&nbsp;Maureen Rischmueller ,&nbsp;Yi Tian Ting","doi":"10.1016/j.jtauto.2025.100311","DOIUrl":"10.1016/j.jtauto.2025.100311","url":null,"abstract":"<div><div>Sjögren's disease (SjD) is a chronic systemic autoimmune disorder characterised by lymphocytic infiltration of the salivary and lacrimal glands, leading to the hallmark symptoms of dry eyes and dry mouth. Beyond glandular dysfunction, many patients experience systemic complications—including B cell hyperactivity, organ-specific inflammation, and a markedly increased risk of non-Hodgkin lymphoma—that are frequently under-recognised and poorly managed. Current treatments remain largely empirical and symptomatic, with limited efficacy in modifying disease progression or restoring immune tolerance.</div><div>Recent advances have illuminated profound dysregulation in both innate and adaptive immunity, revealing novel therapeutic targets now under investigation in clinical trials, including type I interferon signalling, B cell activation, and co-stimulatory pathways. Central to this dysregulation is T cell–driven pathology: CD8⁺ T cell cytotoxicity, defective regulatory T cell (Treg) function, and HLA class II–mediated presentation of self-antigens to autoreactive CD4⁺ T cells are key mechanisms in disease initiation and persistence.</div><div>A growing body of evidence implicates Ro autoantigens—Ro60 and Ro52—as central targets in SjD pathogenesis. Anti-Ro antibodies are present in approximately 70 % of patients and serve as both diagnostic markers and indicators of systemic involvement. Ro antigens and their corresponding antibodies are consistently detected in inflamed salivary tissues, underscoring their potential as compelling targets for antigen-specific therapy.</div><div>This review examines the immunopathogenic role of Ro-specific T cell responses in SjD and outlines how engineered Treg-based therapies may enable precise immune modulation, restore tolerance, and provide durable disease control for patients with this complex autoimmune condition.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100311"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical efficacy and immunomodulation of double-filtration plasmapheresis in autoimmune encephalitis: A prospective study highlighting the importance of timely initiation","authors":"Hongyan Li ,&nbsp;Kan Wang ,&nbsp;Qiuju Li ,&nbsp;Xuzhong Pei ,&nbsp;Jie Ding ,&nbsp;Jing Peng ,&nbsp;Wanwan Li ,&nbsp;Xiajun Zhou ,&nbsp;Desheng Zhu ,&nbsp;Yangtai Guan","doi":"10.1016/j.jtauto.2025.100318","DOIUrl":"10.1016/j.jtauto.2025.100318","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Double-filtration plasmapheresis (DFPP) has emerged as a plasma-saving alternative to therapeutic plasma exchange for autoimmune encephalitis (AE), but prospective evidence regarding its dual effects on both clinical efficacy and immunomodulation remains limited. This study aimed to evaluate the clinical and immunological effects of DFPP in AE.</div></div><div><h3>Methods</h3><div>In this prospective single-center cohort study, 57 patients diagnosed with AE according to international criteria were enrolled between 2018 and 2023. Participants received DFPP (median 3–5 sessions), either alone or combined with immunotherapies. The primary outcome was neurological improvement, measured by the change in modified Rankin Scale (ΔmRS). Secondary outcomes included symptomatic change (ΔCASE score), immunological parameter shifts, and adverse events. Subgroup analyses were conducted based on antibody type, treatment timing, and combination therapies.</div></div><div><h3>Results</h3><div>The cohort had a median age of 47 years (IQR: 24–65), with 49.1 % being female. DFPP significantly reduced median mRS scores from 3.00 to 1.00 (<em>p</em> &lt; 0.001) and CASE scores from 3.00 to 1.00 (<em>p</em> &lt; 0.001). The overall functional improvement rate was 71.9 %. Initiation of DFPP within 14 days of symptom onset was associated with significantly higher response rates (100 % vs. 63.6 %, <em>p</em> &lt; 0.05) and greater neurological improvement (<em>p</em> &lt; 0.05). Combination with IVMP or IVIG did not enhance efficacy compared to DFPP alone (<em>p</em> = 0.600). Immunological profiling revealed significant reductions in IgG (77.55 %), IgA (76.11 %), and IgM (79.96 %), along with modulation of lymphocyte subsets and cytokine levels. Adverse events occurred in 28.1 % of patients, predominantly mild catheter-related thrombosis.</div></div><div><h3>Conclusions</h3><div>DFPP is an effective and well-tolerated treatment for autoimmune encephalitis, significantly improving neurological function modulates immune responses.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100318"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprint","authors":"Georgios K. Vasileiadis ,&nbsp;Yuan Zhang ,&nbsp;Marion Laudette ,&nbsp;Tahzeeb Fatima ,&nbsp;Anna-Karin Hultgård Ekwall ,&nbsp;Reshmi Sureshkumar ,&nbsp;Ronald van Vollenhoven ,&nbsp;Jon Lampa ,&nbsp;Bjorn Gudbjornsson ,&nbsp;Espen A. Haavardsholm ,&nbsp;Dan Nordström ,&nbsp;Gerdur Gröndal ,&nbsp;Kim Hørslev-Petersen ,&nbsp;Kristina Lend ,&nbsp;Merete L. Hetland ,&nbsp;Michael Nurmohamed ,&nbsp;Mikkel Østergaard ,&nbsp;Till Uhlig ,&nbsp;Tuulikki Sokka-Isler ,&nbsp;Anna Rudin ,&nbsp;Cristina Maglio","doi":"10.1016/j.jtauto.2025.100310","DOIUrl":"10.1016/j.jtauto.2025.100310","url":null,"abstract":"<div><h3>Objective</h3><div>In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) alter their metabolism to support their activation. We aimed to analyse the full spectrum of metabolic alterations associated with RA by performing untargeted metabolomics in RA FLS vs. non-inflamed (NI) FLS.</div></div><div><h3>Methods</h3><div>Untargeted annotated metabolomics was performed using mass spectrometry on ten primary RA and seven NI FLS culture extracts and 220 serum samples from participants with early RA from the randomised controlled NORD-STAR trial. Carnitine-related proteins were measured with Western blot. FLS bioenergetic profile was assessed with a Seahorse flux analyser.</div></div><div><h3>Results</h3><div>Metabolomics analysis based on 138 annotated metabolites revealed a distinct metabolic fingerprint between RA and NI FLS. Of the 12 metabolites enriched in RA FLS, 11 were acylcarnitines. Pro-inflammatory stimulation of NI FLS also led to acylcarnitine accumulation. RA FLS exhibited lower levels of CD36, a fatty acid transporter, but similar levels of L-carnitine transporter, and carnitine palmitoyltransferase 1 A and 2 compared to NI FLS. Seahorse analyses showed no difference in fatty acid oxidation between RA and NI FLS; however, RA FLS displayed mitochondrial dysfunction and energetic impairment. Serum acylcarnitine content decreased after 24 weeks of treatment with methotrexate combined with abatacept or tocilizumab in patients with early RA achieving remission.</div></div><div><h3>Conclusion</h3><div>Acylcarnitine accumulation is a characteristic of RA FLS metabolic fingerprint and could be linked to mitochondrial dysfunction. In patients with early RA, acylcarnitine content in serum decreases after successful anti-rheumatic treatment. These results indicate a dysregulation in acylcarnitine metabolism in RA at the joint level and systemically.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100310"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144878752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging cell-based and cell-free therapeutic strategies for vitiligo","authors":"Nasser Gholijani ,&nbsp;Effat Noori ,&nbsp;Zeinab Zarei-Behjani ,&nbsp;Delsuz Rezaee ,&nbsp;Maryam Khodaei ,&nbsp;Gholamhossien Darya ,&nbsp;Kobra Mehdinejadiani ,&nbsp;Zeinab Dehghan","doi":"10.1016/j.jtauto.2025.100331","DOIUrl":"10.1016/j.jtauto.2025.100331","url":null,"abstract":"<div><div>Vitiligo is a chronic, acquired skin disorder characterized by the loss of pigmentation due to the destruction or dysfunction of melanocytes. Conventional treatments such as corticosteroids and phototherapy often produce limited and unpredictable outcomes. In recent years, novel therapeutic strategies—including both cell-based and cell-free approaches such as melanocyte transplantation, mesenchymal stem cells (MSCs), platelet-rich plasma (PRP), stem cell secretome, and exosomes—have emerged as promising alternatives. These therapies aim to restore pigmentation by replenishing melanocytes, modulating immune responses, and mitigating oxidative stress. This review explores the mechanisms of action, clinical efficacy, and translational challenges associated with each approach. While melanocyte transplantation demonstrates the highest repigmentation success in stable cases, stem cell- and exosome-based therapies offer significant potential for personalized and long-term treatment of vitiligo.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100331"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond conventional treatment: Novel cell therapies for systemic lupus erythematosus","authors":"Zeinab Zarei-Behjani ,&nbsp;Arghavan Hosseinpouri ,&nbsp;Maryam Fotoohi ,&nbsp;Akram Shafiee ,&nbsp;Dorna Asadi","doi":"10.1016/j.jtauto.2025.100308","DOIUrl":"10.1016/j.jtauto.2025.100308","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by its heterogeneity, as it can affect various organs and exhibit a diverse clinical progression. The identification of SLE relies on the presence of distinct clinical manifestations in the skin, joints, kidneys, and the central nervous system, along with serological markers like antinuclear antibodies such as antibodies targeting dsDNA. The present therapeutic approaches for SLE encompass the use of antimalarial agents, glucocorticoids, immunosuppressive medications, and biological therapies. Despite the advancements in therapeutic strategies, SLE continues to be linked with adverse outcomes. The complicity and unpredictable nature of disease, characterized by episodes of relapses and remissions, coupled with the side effects of current treatment options, the progressive accumulation of organ damage, and persistent mortality rates despite therapeutic improvements, underscores the urgent necessity for the creation of innovative, effective, and specifically targeted therapies. Cell-based therapies, although still in their nascent stages, have attracted considerable interest in the realm of SLE treatment due to their potential for long-term disease suppression or even the possibility of a cure. Various cell types have emerged as promising candidates for SLE management. This review aims to provide a brief overview of the most recent research on novel cell-based therapeutic approaches that have progressed to either pre-clinical or clinical trial phases for the treatment of SLE.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100308"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to ‘Emerging cell-based and cell-free therapeutic strategies for vitiligo’ [J. Transl. Autoimmun., 11 (2025), 100331]","authors":"Nasser Gholijani ,&nbsp;Effat Noori ,&nbsp;Zeinab Zarei-Behjani ,&nbsp;Delsuz Rezaee ,&nbsp;Maryam Khodaei ,&nbsp;Gholamhossien Darya ,&nbsp;Kobra Mehdinejadiani ,&nbsp;Zeinab Dehghan","doi":"10.1016/j.jtauto.2025.100335","DOIUrl":"10.1016/j.jtauto.2025.100335","url":null,"abstract":"","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100335"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cre-driven tdTomato expression unexpectedly confers resistance to peripheral but not central lupus in dLckCre mice","authors":"Ning Han ,&nbsp;Keer Wang ,&nbsp;Dan Yang ,&nbsp;Mingxuan Han,&nbsp;Xiaoxiao Hou,&nbsp;Zhenghao Xu","doi":"10.1016/j.jtauto.2025.100320","DOIUrl":"10.1016/j.jtauto.2025.100320","url":null,"abstract":"<div><div>The Cre-driven tdTomato reporter system is widely used to visualize gene expression and cellular dynamics. Here we tested the impact of the tdTomato reporter system on the progression of both central and peripheral manifestations of systemic lupus erythematosus (SLE) in dLckCre mice. We crossed dLckCre mice with ROSA26^floxed^{^-}^{Stop-tdTomato} mice to generate conditional dLck-driven tdTomato reporter mice (DT mice). Then, SLE models were induced by pristane injection in DT mice or by crossing DT mice with B6/lpr mice. Central and peripheral manifestations of SLE were assessed. Surprisingly, we found that DT mice exhibited a significant reduction in the progression of peripheral manifestations of SLE, evidenced by decreased severity of lymph node and splenic lesions, and improved renal pathology. However, DT mice showed similar central manifestations of SLE as control mice, evidenced by similar behavioral performance, CD4⁺ T cell infiltration in the choroid plexus, and microglial activation in the hippocampus. Flow cytometry revealed a significant reduction in the proportion of double-negative (DN) T cells in the peripheral blood of DT mice. Immunofluorescence analysis confirmed no significant differences in microglial morphology or choroid plexus CD4⁺ T cell infiltration between DT lupus mice and control mice. Notably, over 80 % of the infiltrating lymphocytes in the choroid plexus of lupus mice were CD4⁺ T cells. Adoptive transfer experiments further confirmed that these ectopically aggregated CD4⁺ T cells in the choroid plexus constitute a key pathogenic factor driving the onset and progression of neuropsychiatric SLE (NPSLE). Thus, conditional tdTomato expression alleviated peripheral but not central manifestations of SLE in dLckCre mice, suggesting a diverse role of dLck-labeled T lymphocytes in SLE development. Our results also provide additional evidence supporting the existence of a distinct separation mechanism between peripheral and central manifestations of SLE.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100320"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}