AP-1-independent NFAT signaling maintains follicular T cell function in infection and autoimmunity.

Autor:	Seth A; Department of Internal Medicine, Section of Rheumatology, Allergy and Immunology, School of Medicine, Yale University , New Haven, CT, USA., Yokokura Y; Department of Internal Medicine, Section of Rheumatology, Allergy and Immunology, School of Medicine, Yale University , New Haven, CT, USA., Choi JY; Department of Internal Medicine, Section of Rheumatology, Allergy and Immunology, School of Medicine, Yale University , New Haven, CT, USA., Shyer JA; Department of Immunobiology, School of Medicine, Yale University , New Haven, CT, USA., Vidyarthi A; Department of Internal Medicine, Section of Rheumatology, Allergy and Immunology, School of Medicine, Yale University , New Haven, CT, USA., Craft J; Department of Internal Medicine, Section of Rheumatology, Allergy and Immunology, School of Medicine, Yale University , New Haven, CT, USA.; Department of Immunobiology, School of Medicine, Yale University , New Haven, CT, USA.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2023 May 01; Vol. 220 (5). Date of Electronic Publication: 2023 Feb 23.
DOI:	10.1084/jem.20211110
Abstrakt:	Coordinated gene expression programs enable development and function of T cell subsets. Follicular helper T (Tfh) cells coordinate humoral immune responses by providing selective and instructive cues to germinal center B cells. Here, we show that AP-1-independent NFAT gene expression, a program associated with hyporesponsive T cell states like anergy or exhaustion, is also a distinguishing feature of Tfh cells. NFAT signaling in Tfh cells, maintained by NFAT2 autoamplification, is required for their survival. ICOS signaling upregulates Bcl6 and induces an AP-1-independent NFAT program in primary T cells. Using lupus-prone mice, we demonstrate that genetic disruption or pharmacologic inhibition of NFAT signaling specifically impacts Tfh cell maintenance and leads to amelioration of autoantibody production and renal injury. Our data provide important conceptual and therapeutic insights into the signaling mechanisms that regulate Tfh cell development and function. (© 2023 Seth et al.)
Databáze:	MEDLINE
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