Role of Btn2a2 in central tolerance induction mechanisms

• Applicants: Dr. Kerstin Sarter-Zaiss; Professor Dr. Mario M. Zaiss
• Subject Area: Immunology ; Rheumatology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 543936725

Butyrophilins (BTN) are a family of transmembrane proteins belonging to the immunoglobulin superfamily of proteins. Emerging data pointing to a role in regulating T cell activation have stimulated considerable interest in studying the various members of the BTN family. The murine members, Btn1a1 and Btn2a2, were both shown to inhibit the activation of T cells in vitro. We could show that Btn2a2-deficient mice exhibit exacerbated experimental autoimmune encephalomyelitis accompanied by enhanced T cell activation and proliferation, consistent with an inhibitory role of Btn2a2. However, the effect of Btn2a2 on developing T cells in the thymus (thymocytes) has not been addressed. Strikingly, aged Btn2a2-deficient mice displayed elevated titers auf autoantibodies, suggesting a defect in tolerance mechanisms. Intrigued by this finding, we characterized the expression of Btn2a2 in the thymus and its effect on thymocytes. Based on here presented preliminary experiments we hypothesize that Btn2a2 impacts on thymocytes during both cortical and medullary thymocyte selection leading to a biased T cell repertoire prone to inciting autoimmunity.

• DFG Programme: Research Grants