Reference - Detail
| RRC ID | 89237 |
|---|---|
| Author | Takeshita M, Inamo J, Wakui S, Nagashima R, Nishino T, Tsunoda K, Usuda S, Inokuchi H, Ishigaki K, Sasaki T, Kagoya Y, Suzuki K, Kaneko Y. |
| Title | Identification of a shared antigen linking CD4+ T and B cell pathology in Sjögren's disease. |
| Journal | Sci Adv |
| Abstract |
Sjögren's disease (SjD) is an autoimmune disorder characterized by lymphocytic infiltration of exocrine glands. Although B cells producing anti-Ro60 autoantibodies are frequently found in salivary gland lesions, the antigen specificity of CD4+ T cells has remained unclear. Given accumulating evidence for T cell involvement in local autoantibody production, we comprehensively investigated Ro60 reactivity among lesion-infiltrating CD4+ T cells. Over 200 T cell receptors (TCRs) enriched in salivary glands from Japanese and Caucasian patients with SjD were screened using a TCR reporter system, identifying 13 Ro60-reactive TCRs predominantly expressed in T peripheral helper/T follicular helper subset, along with human leukocyte antigen alleles linked to SjD susceptibility. Ro60 was efficiently phagocytosed by antigen-presenting cells in the presence of autoantibodies and presented to Ro60-specific T cells, triggering their activation. This suggests that Ro60-specific B and CD4+ T cells orchestrate a pathological loop in salivary glands. Our study provides the first molecular identification of a major CD4+ T cell antigen in systemic autoimmunity and highlights coordinated T-B cell responses against a shared autoantigen. |
| Volume | 12(23) |
| Pages | eaeb2491 |
| Published | 2026-6-5 |
| DOI | 10.1126/sciadv.aeb2491 |
| PMID | 42234741 |
| PMC | PMC13232566 |
| MeSH | Autoantibodies / immunology Autoantigens* / immunology B-Lymphocytes* / immunology B-Lymphocytes* / metabolism B-Lymphocytes* / pathology CD4-Positive T-Lymphocytes* / immunology CD4-Positive T-Lymphocytes* / metabolism CD4-Positive T-Lymphocytes* / pathology Humans Lymphocyte Activation / immunology RNA, Small Cytoplasmic / immunology Receptors, Antigen, T-Cell / genetics Receptors, Antigen, T-Cell / immunology Receptors, Antigen, T-Cell / metabolism Ribonucleoproteins / immunology SS-A Antigen Salivary Glands / immunology Salivary Glands / metabolism Salivary Glands / pathology Sjogren's Syndrome* / immunology Sjogren's Syndrome* / metabolism Sjogren's Syndrome* / pathology |
| IF | 13.117 |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 38 |
| Altmetric score changes over past 6months | 50.6 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) |