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Age-associated CD4+ T cells with B cell-promoting functions are regulated by ZEB2 in autoimmunity.
Goto, Manaka; Takahashi, Hideyuki; Yoshida, Ryochi; Itamiya, Takahiro; Nakano, Masahiro; Nagafuchi, Yasuo; Harada, Hiroaki; Shimizu, Toshiaki; Maeda, Meiko; Kubota, Akatsuki; Toda, Tatsushi; Hatano, Hiroaki; Sugimori, Yusuke; Kawahata, Kimito; Yamamoto, Kazuhiko; Shoda, Hirofumi; Ishigaki, Kazuyoshi; Ota, Mineto; Okamura, Tomohisa; Fujio, Keishi.
Afiliación
  • Goto M; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Takahashi H; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Yoshida R; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Itamiya T; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Nakano M; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Nagafuchi Y; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Harada H; Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
  • Shimizu T; Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
  • Maeda M; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Kubota A; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Toda T; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Hatano H; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Sugimori Y; Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Kawahata K; Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Yamamoto K; Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Shoda H; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Ishigaki K; Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
  • Ota M; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
  • Okamura T; Department of Rheumatology and Allergology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
  • Fujio K; Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
Sci Immunol ; 9(93): eadk1643, 2024 Mar 29.
Article en En | MEDLINE | ID: mdl-38330141
ABSTRACT
Aging is a significant risk factor for autoimmunity, and many autoimmune diseases tend to onset during adulthood. We conducted an extensive analysis of CD4+ T cell subsets from 354 patients with autoimmune disease and healthy controls via flow cytometry and bulk RNA sequencing. As a result, we identified a distinct CXCR3midCD4+ effector memory T cell subset that expands with age, which we designated "age-associated T helper (THA) cells." THA cells exhibited both a cytotoxic phenotype and B cell helper functions, and these features were regulated by the transcription factor ZEB2. Consistent with the highly skewed T cell receptor usage of THA cells, gene expression in THA cells from patients with systemic lupus erythematosus reflected disease activity and was affected by treatment with a calcineurin inhibitor. Moreover, analysis of single-cell RNA sequencing data revealed that THA cells infiltrate damaged organs in patients with autoimmune diseases. Together, our characterization of THA cells may facilitate improved understanding of the relationship between aging and autoimmune diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Lupus Eritematoso Sistémico Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Humans Idioma: En Revista: Sci Immunol Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Lupus Eritematoso Sistémico Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Humans Idioma: En Revista: Sci Immunol Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos