Regulation of innate lymphocyte function by Zbtb32

 描述（由申请人提供）：免疫系统通过免疫细胞和分泌因子的复杂相互作用对感染做出反应，目的是消除入侵的病原体并修复受损组织。先天性淋巴细胞包括NK细胞、NKT细胞、巨噬细胞T细胞和新发现的先天性淋巴样细胞（ILC），是一种有趣且研究相对不足的免疫细胞亚群，在先天性和适应性免疫应答的界面发挥作用。我的目标是建立一个独立的研究项目，专注于了解在感染过程中调节先天淋巴细胞效应反应的分子途径。 在我的博士后培训期间，我发现了一种涉及转录因子Zbtb 32和Blimp-1的新型信号传导途径，该途径关键性地调节NK细胞的抗病毒反应1。作为一名独立的研究人员，我计划继续研究Zbtb 32如何调节先天淋巴细胞的抗病原体反应。具体地，在该K22申请中提出的研究旨在：（1）确定Zbtb 32和Blimp-1是否在NK细胞中物理相互作用以及Zbtb 32是否影响Blimp- 1靶向的用于转录抑制的基因组;以及（2）探索Zbtb 32是否在体内流感感染期间调节2型ILC的抗病毒免疫应答。 鉴于先天淋巴细胞调节的疾病范围广泛，包括病毒，细菌和蠕虫感染，以及过敏性和自身免疫性疾病，拟议的研究将在开发新疗法，疫苗和诊断测试中具有重要的应用。此外，从这个K22奖的支持将为我提供关键的时间和资源，成功地过渡到终身教职，并获得知识和数据，我将需要启动一个富有成效的和可持续的独立研究生涯。

 DESCRIPTION (provided by applicant): The immune system responds to infection with a complex interplay of immune cells and secreted factors aimed at eliminating the intruding pathogen and repairing damaged tissue. Innate lymphocytes, which include NK cells, NKT cells, T cells, and the newly discovered innate lymphoid cells (ILCs), are a fascinating and relatively understudied subset of immune cells that function at the interface of innate and adaptive immune responses. My goal is to establish independent research program focused on understanding the molecular pathways that regulate effector responses by innate lymphocytes during infection. During my postdoctoral training, I discovered a novel signaling pathway involving the transcription factors Zbtb32 and Blimp-1 that critically regulates anti-viral responses by NK cells1. As an independent faculty researcher, I plan to continue my investigation of how Zbtb32 regulates anti-pathogen responses by innate lymphocytes. Specifically, the studies proposed in this K22 application aim to: (1) determine whether Zbtb32 and Blimp-1 physically interact in NK cells and whether Zbtb32 influences the suite of genes targeted by Blimp- 1 for transcriptional repression; and (2) explore whether Zbtb32 regulates anti-viral immune responses by Type 2 ILCs during influenza infection in vivo. Given the remarkable range of diseases regulated by innate lymphocytes, including viral, bacterial, and helminth infections, and allergic and autoimmune diseases, the proposed studies will have important applications in the development of new therapies, vaccines, and diagnostic tests for a wide variety of human illnesses. Moreover, support from this K22 award would provide me with key time and resources to successfully transition into a tenure-track faculty position and to acquire the knowledge and data I will need to launch a productive and sustainable independent research career.