Transcriptional regulation of T cell quiescence and activation

描述（由申请人提供）：外周幼稚T淋巴细胞的静止状态被认为是由于缺乏激活信号。然而，最近的研究表明，T细胞的静止不是默认的，而是由细胞的外在和内在机制积极维持的，而在转录水平上对其知之甚少。叉头盒蛋白（FOX）是一个在发育、衰老和癌症中具有多种功能的转录因子大家族。最近，我们发现转录因子Foxp1对幼稚T细胞的静止发挥重要的细胞内在调节作用，为成熟T细胞的静止被积极维持提供了直接证据。同时，我们新的初步研究也开始揭示Foxp1的转录网络在激动剂诱导中起重要作用

DESCRIPTION (provided by applicant): The quiescent state of peripheral naive T lymphocytes was thought to be due to the lack of activation signals. Recent studies, however, have shown that T cell quiescence is not by default but actively maintained by both cell extrinsic and intrinsic mechanisms, about which little is known at the transcriptional level. Forkhead box (FOX) proteins comprise a large family of transcription factors with diverse functions in development, aging and cancer. Recently we discovered that transcription factor Foxp1 exerts essential cell-intrinsic regulation of the quiescence of naive T cells, providing direct evidence that mature T cell quiescence is actively maintained. Meanwhile, our new preliminary studies also start to reveal that Foxp1 transcriptional network plays an important role in agonist- induced T cell activation. In this proposal, we will combine various approaches to identify functional targets and molecular pathways regulated by Foxp1 in controlling T cell quiescence, and to define the critical roles of Foxp1 in antigen-induced T cell activation and responses in vivo. Knowledge obtained from these studies will provide information for the design of new therapeutic strategies that would manipulate T cell activation status for the treatment of autoimmune and infectious diseases, and aid in vaccine development. PUBLIC HEALTH RELEVANCE: Recent studies have shown that T cell quiescence is not by default but actively maintained by both cell extrinsic and intrinsic mechanisms, about which little is known at the molecular level. The research on understanding the transcriptional regulation of T cell quiescence by key factors will provide mechanistic insights to guide the design of new therapeutic strategies that would manipulate T cell activation status for the treatment of autoimmune and infectious diseases, and aid in vaccine development.