Regulation of innate lymphocyte function by Zbtb32

 描述(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来应对感染，旨在消除入侵的病原体和修复受损的组织。天然淋巴细胞包括NK细胞、NKT细胞、T细胞和新发现的天然淋巴样细胞(ILCs)，是一类在天然免疫反应和获得性免疫反应的交界处发挥作用的免疫细胞亚群，研究相对较少。我的目标是建立独立的研究计划，专注于了解在感染过程中通过固有淋巴细胞调节效应器反应的分子途径。 在博士后培训期间，我发现了一条新的信号通路，涉及转录因子Zbtb32和Blimp-1，它关键地调节NK细胞1的抗病毒反应。作为一名独立的学院研究员，我计划继续我的研究，研究Zbtb32如何通过先天性淋巴细胞调节抗病原体反应。具体地说，在这项K22申请中提出的研究旨在：(1)确定Zbtb32和Blimp-1是否在NK细胞中物理上相互作用，以及Zbtb32是否影响Blimp-1靶向转录抑制的一系列基因；以及(2)探索Zbtb32是否调节体内感染流感期间2型ILCs的抗病毒免疫反应。 鉴于先天性淋巴细胞调节的疾病范围广泛，包括病毒、细菌和蠕虫感染，以及过敏和自身免疫性疾病，拟议的研究将在开发新的治疗方法、疫苗和诊断测试广泛的人类疾病方面具有重要应用。此外，来自K22奖项的支持将为我提供关键的时间和资源，让我成功过渡到终身教职，并获得我启动富有成效和可持续的独立研究生涯所需的知识和数据。

 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.