Haljasorg Uku, Dooley James, Laan Martti, Kisand Kai, Bichele Rudolf, Liston Adrian, Peterson Pärt
Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia; and
Department of Microbiology and Immunology, KU Leuven, Leuven 3000, Belgium.
J Immunol. 2017 Mar 1;198(5):1952-1960. doi: 10.4049/jimmunol.1601698. Epub 2017 Jan 20.
The thymus is a primary lymphoid organ required for the induction and maintenance of central tolerance. The main function of the thymus is to generate an immunocompetent set of T cells not reactive to self. During negative selection in the thymus, thymocytes with autoreactive potential are either deleted or differentiated into regulatory T cells (Tregs). The molecular basis by which the thymus allows high-efficiency Treg induction remains largely unknown. In this study, we report that IFN regulatory factor 4 (Irf4) is highly expressed in murine thymic epithelium and is required to prime thymic epithelial cells (TEC) for effective Treg induction. TEC-specific Irf4 deficiency resulted in a significantly reduced thymic Treg compartment and increased susceptibility to mononuclear infiltrations in the salivary gland. We propose that Irf4 is imperative for thymic Treg homeostasis because it regulates TEC-specific expression of several chemokines and costimulatory molecules indicated in thymocyte development and Treg induction.
胸腺是诱导和维持中枢耐受所必需的主要淋巴器官。胸腺的主要功能是产生一组对自身无反应的具有免疫活性的T细胞。在胸腺中的阴性选择过程中，具有自身反应潜能的胸腺细胞要么被清除，要么分化为调节性T细胞（Tregs）。胸腺实现高效诱导Tregs的分子基础在很大程度上仍不清楚。在本研究中，我们报告干扰素调节因子4（Irf4）在小鼠胸腺上皮中高表达，并且是启动胸腺上皮细胞（TEC）以有效诱导Tregs所必需的。TEC特异性Irf4缺陷导致胸腺Treg区室显著减少，并增加了对唾液腺单核浸润的易感性。我们提出，Irf4对胸腺Treg稳态至关重要，因为它调节胸腺细胞发育和Treg诱导中所示的几种趋化因子和共刺激分子的TEC特异性表达。
