Age-associated CD4 + T cells with B cell-promoting functions are regulated by ZEB2 in autoimmunity.

Autor: 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.; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan., Nakano M; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.; Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.; Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan., Nagafuchi Y; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan., Harada H; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan., Shimizu T; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan., Maeda M; Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan., Kubota A; Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan., Toda T; Department of Neurology, 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.; Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan., Sugimori Y; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan., Kawahata K; Department of Rheumatology and Allergology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan., Yamamoto K; Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 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 Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan., Fujio K; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2024 Mar 29; Vol. 9 (93), pp. eadk1643. Date of Electronic Publication: 2024 Mar 29.
DOI: 10.1126/sciimmunol.adk1643
Abstrakt: 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 CXCR3 mid CD4 + effector memory T cell subset that expands with age, which we designated "age-associated T helper (T H A) cells." T H A 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 T H A cells, gene expression in T H A 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 T H A cells infiltrate damaged organs in patients with autoimmune diseases. Together, our characterization of T H A cells may facilitate improved understanding of the relationship between aging and autoimmune diseases.
Databáze: MEDLINE