Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-Universiät Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
Institute of Biomedical Informatics, Graz University of Technology, Graz, Austria.
J Autoimmun. 2023 Sep;139:103071. doi: 10.1016/j.jaut.2023.103071. Epub 2023 Jun 23.
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.
Butyrophilins 是属于免疫球蛋白超家族的表面受体。虽然该家族的几个成员被牵连到非常规 T 细胞的发育中，但 Butyrophilin 2a2 (Btn2a2) 已被证明抑制常规 T 细胞的激活。在这里，我们证明在稳定状态下，Btn2a2 的主要来源是胸腺上皮细胞 (TEC)。Btn2a2 的缺失改变了胸腺 T 细胞的成熟，并绕过了中枢耐受机制。此外，Btn2a2 小鼠会自发发展出类似于人类原发性干燥综合征 (pSS) 的自身免疫，包括在靶器官中形成三级淋巴结构 (TLS)。在发育中的胸腺细胞上的 Btn2a2 配体与 TCR 信号转导和 CD5 水平降低有关，而 Btn2a2 的缺失导致 TCR 信号转导和 CD5 水平增加。这些结果定义了 Btn2a2 通过调节 TCR 信号强度促进中枢耐受的新作用，并表明了 pSS 发展的潜在机制。
