Cyril Seillet
University of Melbourne, Australia
Title: Complementarity and redundancy of IL-22-producing innate lymphoid cells
Biography
Biography: Cyril Seillet
Abstract
The gastrointestinal tract is the largest surface area in the body and forms the major protective barrier. Dysregulation of this mucosal barrier leads to the development of chronic intestinal disorders such as inflammatory bowel disease. Innate lymphoid cells (ILCs) are early effectors of mucosal immunity and are essential to maintain intestinal homeostasis in the gut. Intestinal T-cells and group 3 innate lymphoid (ILC3) cells control the composition of the microbiota and gut immune responses. Within the gut, ILC3 subsets coexist that either express or lack the natural cytoxicity receptor (NCR) NKp46. We identified here the transcriptional signature associated with the transcription factor T-bet-dependent differentiation of NCR(-) ILC3 cells into NCR(+) ILC3 cells. Contrary to the prevailing view, we found by conditional deletion of the key ILC3 genes Stat3, Il22, Tbx21 and Mcl1 that NCR(+) ILC3 cells were redundant for the control of mouse colonic infection with Citrobacter rodentium in the presence of T-cells. However, NCR(+) ILC3 cells were essential for cecal homeostasis. Our data show that interplay between intestinal ILC3 cells and adaptive lymphocytes results in robust complementary failsafe mechanisms that ensure gut homeostasis.