1 LT β R - independent development of intestinal IL - 22 - producing NKp 46 + innate lymphoid cells

The natural cytotoxicity receptor NKp46 (encoded by Ncr1) is an activating receptor expressed by innate lymphoid cells (ILC), including NK cells, a subset of γδ T cells and intestinal RORγt IL-22 cells (NCR22 cells). Previous studies have proposed a critical role for NCR22 cells in mucosal barrier function through IL-22-mediated production of anti-bacterial peptides from intestinal epithelial cells. Lymphoid tissue inducer (LTi) cells are RORγt ILCs that orchestrate programmed and inducible lymphoid tissue development (including lymph nodes (LN), Peyer’s patches (PP) and intestinal isolated lymphoid follicles from cryptopatches (CP)) through cell-surface expressed lymphotoxin (LT)α1β2 heterotrimers. While LTi and NCR22 cells share phenotypic and functional characteristics, their relationship remains unclear, and a model of CP-dependent development of NCR22 cells from LTi cells has been proposed. Here we test this model using LTβR-deficient Ncr1 mice (that lack all LN, PP and CP). We find that NCR22 cells develop normally in the absence of LTβR, achieving functional competence and a normal tissue localization in the lamina propria. These results indicate that organized lymphoid tissue structures are not requisite for the generation of the intestinal NCR22 cell compartment and suggest a dichotomy in the biological roles of LTi and NCR22 cells.