Contribution of Innate-like Tregs for Preventing Tissue Inflammation

摘要 行政补充摘要： 部分基于我们在亲本R01下进行的研究，我们现在认识到T细胞亚群 具有独特的、与生俱来的效应器功能，导致其他免疫细胞的修改。这些效应器 功能直接由主调控因子BTB-ZF转录因子激活。PLZF(ZBTB16)基因的表达 例如，自然杀伤T细胞持续产生IL-4，这直接影响朴素CD8 T的功能 细胞。我们目前的研究发现的先天类Tregs会影响组织内稳态和巨噬细胞 通过持续释放IL-10发挥作用。我们最新的研究发现了另一种BTB-ZF基因 我们假设控制人类CD8 T细胞亚群的功能。本报告中提出的实验 行政补充将分析淋巴细胞在应答中表达这些转录因子 SARS-CoV-2。致命的感染被认为是先天免疫反应不足的结果。 相反，可导致多器官炎症综合征(MIS)的破坏性细胞因子风暴被认为是 至少在一定程度上，这是由于过度热心的先天免疫反应。与生俱来的参与 淋巴细胞尚未被考虑或评估。

Abstract Summary for administrative supplement: Based in part our studies performed under the parent R01, we now recognize that subpopulations of T cells have distinct, innate-like effector functions that lead to the modification of other immune cells. These effector functions are directly enabled by master regulator BTB-ZF transcription factors. PLZF (ZBTB16) expressing natural killer T cells, for example, continuously produce IL-4, which directly impacts the function of naïve CD8 T cells. The innate-like Tregs identified by our current studies, impact tissue homeostasis and macrophage function by the continuous release of IL-10. Our most recent studies have identified yet another BTB-ZF gene that we hypothesize controls the function of subsets of human CD8 T cells. Experiments proposed in this administrative supplement will analyze lymphocytes expressing these transcription factors in the response to SARS-CoV-2. Fatal infection is hypothesized to be a consequence of an inadequate innate immune response. In contrast, the devasting cytokine storms that lead to multiorgan inflammatory syndrome (MIS) are considered to be due, at least in part, to an overzealous innate immune response. The participation of innate-like lymphocytes has not yet been considered or evaluated.