Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, United States.
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Front Immunol. 2021 Mar 1;12:623280. doi: 10.3389/fimmu.2021.623280. eCollection 2021.
Expression of tissue-restricted antigens (TRAs) in thymic epithelial cells (TECs) ensures negative selection of highly self-reactive T cells to establish central tolerance. Whether some of these TRAs could exert their canonical biological functions to shape thymic environment to regulate T cell development is unclear. Analyses of publicly available databases have revealed expression of transcripts at various levels of many cytokines and cytokine receptors such as IL-15, IL-15Rα, IL-13, and IL-23a in both human and mouse TECs. Ablation of either IL-15 or IL-15Rα in TECs selectively impairs type 1 innate like T cell, such as NKT1 and γδT1 cell, development in the thymus, indicating that TECs not only serve as an important source of IL-15 but also trans-present IL-15 to ensure type 1 innate like T cell development. Because type 1 innate like T cells are proinflammatory, our data suggest the possibility that TEC may intrinsically control thymic inflammatory innate like T cells to influence thymic environment.
组织限制性抗原 (TRAs) 在胸腺上皮细胞 (TECs) 中的表达确保了高度自身反应性 T 细胞的阴性选择，从而建立中枢耐受。这些 TRA 中的一些是否能够发挥其典型的生物学功能来塑造胸腺微环境以调节 T 细胞发育尚不清楚。对公共可用数据库的分析表明，在人和小鼠 TECs 中，多种细胞因子和细胞因子受体（如 IL-15、IL-15Rα、IL-13 和 IL-23a）的转录本以不同水平表达。TEC 中 IL-15 或 IL-15Rα 的缺失选择性地损害了 1 型固有样 T 细胞（如 NKT1 和 γδT1 细胞）在胸腺中的发育，表明 TEC 不仅是 IL-15 的重要来源，而且还转呈 IL-15 以确保 1 型固有样 T 细胞的发育。由于 1 型固有样 T 细胞具有促炎作用，我们的数据表明 TEC 可能内在地控制胸腺炎症固有样 T 细胞，从而影响胸腺微环境。
