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.
Original language | English |
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Article number | 103071 |
Journal | Journal of Autoimmunity |
Volume | 139 |
DOIs | |
Publication status | Published - Sept 2023 |
Keywords
- Autoimmune disease
- Autoimmunity
- Butyrophilin 2a2 (Btn2a2)
- Central tolerance
- Primary sjögren's syndrome (pSS)
- Thymic epithelial cells (TEC)
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology