Regulatory T cells (Tregs) represent a major population in the control of immune homeostasis and autoimmunity. Here we show that Fos-like 2 (Fosl2), a TCR-induced AP1 transcription factor, represses Treg development and controls autoimmunity. Mice overexpressing Fosl2 (Fosl2^tg) indeed show a systemic inflammatory phenotype, with immune infiltrates in multiple organs. This phenotype is absent in Fosl2^tg × Rag2^−/− mice lacking T and B cells, and Fosl2 induces T cell-intrinsic reduction of Treg development that is responsible for the inflammatory phenotype. Fosl2^tg T cells can transfer inflammation, which is suppressed by the co-delivery of Tregs, while Fosl2 deficiency in T cells reduces the severity of autoimmunity in the EAE model. We find that Fosl2 could affect expression of FoxP3 and other Treg development genes. Our data highlight the importance of AP1 transcription factors, in particular Fosl2, during T cell development to determine Treg differentiation and control autoimmunity.

调节性T细胞（Tregs）代表着控制免疫稳态和自身免疫的主要人群。在这里，我们显示了TCR诱导的AP1转录因子Fos-like 2（Fosl2）抑制Treg的发育并控制自身免疫。过表达Fosl2（Fosl2 ^tg）的小鼠确实显示出系统性炎症表型，并且在多个器官中都有免疫浸润。在缺乏T细胞和B细胞的Fosl2 ^tg × Rag2 ^-/-小鼠中不存在这种表型，Fosl2诱导T细胞内在性Treg发育的Treg内在减少，而Treg的形成是炎症性表型的原因。FOSL2 ^TGT细胞可以转移炎症，这可以通过Treg的共同传递来抑制，而T细胞中的Fos12缺乏则可以降低EAE模型中自身免疫的严重程度。我们发现Fosl2可能影响FoxP3和其他Treg发育基因的表达。我们的数据突出了AP1转录因子，特别是Fosl2，在T细胞发育过程中确定Treg分化和控制自身免疫的重要性。