Complementarity and redundancy of IL-22-producing innate lymphoid cells

Intestinal T cells and group 3 innate lymphoid cells (ILC3) control the composition of the microbiota and gut immune responses. Within the gut there coexists ILC3 subsets which either express or lack the Natural cytoxicity receptor (NCR) NKp46. We identify here the transcriptional signature associated with the T-bet-dependent differentiation of NCR(−) ILC3 into NCR(+) ILC3. Contrary to the prevailing view, we show by conditional deletion of the key ILC3 genes Stat3, Il22, Tbx21 and Mcl1 that NCR(+) ILC3 were redundant for the control of mouse colonic infections with Citrobacter rodentium in the presence of T cells. However, NCR(+) ILC3 were essential for cecum homeostasis. Our data show that interplay between intestinal ILC3 and adaptive lymphocytes results in robust complementary fail-safe mechanisms ensuring gut homeostasis.