Natural helper cells in allergic airway inflammation

描述（由申请人提供）：自然辅助性（NH）细胞是新发现的先天免疫细胞，在蠕虫感染或流感感染后产生t -辅助性2型（Th2）细胞因子并促进保护性2型免疫。NH细胞的个体发生及其在过敏性疾病中的功能尚不清楚。引人注目的是，我们发现NH细胞具有与T细胞谱系祖细胞相似的基因表达谱，并且NH细胞的发育依赖于TCF-1，这是早期T细胞发育中必不可少的转录因子。我们建议确定NH细胞发育的分子途径。我们还将研究NH细胞在过敏性哮喘发病机制中的作用。本提案的研究将提高我们对NH细胞的产生和功能的理解，这将为针对NH细胞治疗Th2相关疾病的治疗策略提供信息。

DESCRIPTION (provided by applicant): Natural Helper (NH) cells are newly discovered innate immune cells that produce T-helper type 2 (Th2) cytokines and promote protective type 2 immunity during helminth infection, or after influenza infection. The ontogeny of NH cells and their function in allergic diseases are not known. Strikingly, we find that NH cells have similar gene expression profile as T cell lineage progenitors, and that the development of NH cells is dependent on TCF-1, an essential transcription factor in early T cell development. We propose to determine the molecular pathways that underlie the development of NH cells. We will also examine the role of NH cells in the pathogenesis of allergic asthma. Studies in this proposal will improve our understanding of the generation and function of NH cells, which will inform therapeutic strategies to target NH cells for Th2 associated diseases. PUBLIC HEALTH RELEVANCE: T helper 2 (Th2) cytokines are central players in the pathogenesis of allergic asthma. Natural helper cells are newly discovered immune cells that were shown to be a major source of Th2 cytokines but neither their developmental origin nor their significance in asthma is understood. We propose to identify the cellular precursors and the signals that give rise to Natural helper cells. Using a mouse model we will also determine the role of Natural helper cells in the pathology of allergen-induced airway inflammation. Our study will provide important clues to targeting Natural helper cells as a novel therapeutic approach to Th2-driven (allergic) airway inflammation in asthma.