The Interaction between Lymphoid Tissue Inducer-Like Cells and T Cells in the Mesenteric Lymph Node Restrains Intestinal Humoral Immunity

Lymphoid tissue inducer (LTi)/LTi-like cells are critical for lymphoid organogenesis and regulation of adaptive immunity in various tissues. However, the maintenance and regulation mechanisms of LTi-like cells among different tissues are not clear yet. Here, we find that LTi-like cells from different tissues display heterogeneity. The maintenance of LTi-like cells in the mesenteric lymph node (mLN), but not the gut, requires RANKL signaling from CD4⁺ T cells. LTi-like cells from the mLN, but not the gut, could in turn inhibit the development of T follicular helper cells and subsequent humoral responses during intestinal immunization in an ID2- and PD-L1-dependent manner. Together, our findings implicate that the interaction between LTi-like cells and T cells in the mLN could precisely control the intestinal mucosal adaptive immune response.