APCs and environmental cues for inflammation-linked Th17 immunity

工作概要 了解抗原呈递细胞（APC）如何使用环境线索影响T细胞抗原 特异性和功能是一个紧迫的问题，因为产生IL-17的CD 4 T细胞（Th 17）可以存在于两个细胞中， 二分状态：1）Th 17，其存在于健康中并且不引起炎症（“Th 17 h”），和2）Th 17，其扩增 在自身免疫性和炎性疾病（“Th 17 i”）期间。因为有些组织，比如小肠， 含有大量的Th 17 h细胞，区分这些组织中的Th 17 h和Th 17 i细胞一直是一个很好的方法。 了不起的挑战因此，Th 17 i细胞的起源、功能甚至存在于这些细胞中， 组织一直备受争议。为了开始解决这个问题，我们重点观察了炎症患者中的Th 17细胞。 小肠和鉴定的Th 17 i细胞群容易与Th 17 h细胞区分，因为这些 Th 17 i细胞比Th 17 h细胞具有不同的抗原特异性和定位。到目前为止，所有这些措施 Th 17 i细胞是炎症的专属细胞，在健康状况下似乎不存在。选用我们的 Th 17 h和Th 17 i细胞的区分方法，本提案的目的是了解Th 17 h和Th 17 i细胞的性质， Th 17 i细胞的起源，以及支持其在炎症中扩张的环境线索和APC。

Summary of Work Understanding how antigen presenting cells (APCs) use environmental cues to influence T cell antigen specificity and function is a pressing issue since IL-17-producing CD4 T cells (Th17) can exist in two dichotomous states: 1) Th17 that exist in health and cause no inflammation (“Th17h”) and 2) Th17 that expand during autoimmune and inflammatory disease (“Th17i”). Because some tissues, like small intestine, naturally contain large numbers of Th17h cells, distinguishing Th17h and Th17i cells in these tissues has been a remarkable challenge. Consequentially, the origins, functions and even the existence of Th17i cells in these tissues have been highly debated. To begin to resolve this we took a focused look at Th17 cells in inflamed small intestine and identified populations of Th17i cells readily distinguishable from Th17h cells since these Th17i cells have distinct antigen specificity and localization than do Th17h cells. By all measures thus far these Th17i cells are exclusive to inflammation and do not appear to exist in conditions of health. With our new approach to distinguish Th17h and Th17i cells, the objective of this proposal is to understand the nature and origins of Th17i cells, and the environmental cues and APCs underpinning their expansion in inflammation.