Butyrophilin 2a2 (Btn2a2) expression on thymic epithelial cells promotes central T cell tolerance and prevents autoimmune disease: Btn2a2 promotes central tolerance

Frech M, Danzer H, Uchil P, Azizov V, Schmid E, Schälter F, Dürholz K, Mauro D, Rauber S, Munoz Becerra L, Taher L, Ciccia F, Schober K, Irla M, Sarter K, Schett G, Zaiss M (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Journal of Autoimmunity Elsevier

Book Volume: 139

Article Number: 103071

DOI: 10.1016/j.jaut.2023.103071

Abstract

Butyrophilins are surface receptors belonging to the immunoglobulin superfamily. While several members of the butyrophilin family have been implicated in the development of unconventional T cells, butyrophilin 2a2 (Btn2a2) has been shown to inhibit conventional T cell activation. Here, we demonstrate that in steady state, the primary source of Btn2a2 are thymic epithelial cells (TEC). Absence of Btn2a2 alters thymic T cell maturation and bypasses central tolerance mechanisms. Furthermore, Btn2a2−/− mice develop spontaneous autoimmunity resembling human primary Sjögren's Syndrome (pSS), including formation of tertiary lymphoid structures (TLS) in target organs. Ligation of Btn2a2 on developing thymocytes is associated with reduced TCR signaling and CD5 levels, while absence of Btn2a2 results in increased TCR signaling and CD5 levels. These results define a novel role for Btn2a2 in promoting central tolerance by modulating TCR signaling strength and indicate a potential mechanism of pSS development.

Authors with CRIS profile

Michael Frech Department of Medicine 3 – Rheumatology and Immunology Heike Danzer Lehrstuhl für Genetik Pooja Uchil Lehrstuhl für Klinische und Molekulare Virologie Vugar Azizov Department of Medicine 3 – Rheumatology and Immunology Eva Schmid Department of Medicine 3 – Rheumatology and Immunology Kerstin Dürholz Department of Medicine 3 – Rheumatology and Immunology Simon Rauber Department of Medicine 3 – Rheumatology and Immunology Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Kilian Schober Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Kerstin Sarter-Zaiss Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III Mario Zaiss Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Technische Universität Graz AT Austria (AT) Università degli studi della Campania Luigi Vanvitelli IT Italy (IT) Immunology Center of Marseille-Luminy FR France (FR)

How to cite

APA:

Frech, M., Danzer, H., Uchil, P., Azizov, V., Schmid, E., Schälter, F.,... Zaiss, M. (2023). Butyrophilin 2a2 (Btn2a2) expression on thymic epithelial cells promotes central T cell tolerance and prevents autoimmune disease: Btn2a2 promotes central tolerance. Journal of Autoimmunity, 139. https://dx.doi.org/10.1016/j.jaut.2023.103071

MLA:

Frech, Michael, et al. "Butyrophilin 2a2 (Btn2a2) expression on thymic epithelial cells promotes central T cell tolerance and prevents autoimmune disease: Btn2a2 promotes central tolerance." Journal of Autoimmunity 139 (2023).

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