ILCs have effector cytokine profiles similar to those of CD4+ T cells but are much less numerous than are CD4+ T cells. In Nature, Hepworth et al. specifically target RORγt+ ILCs (group 3 ILCs) by genetic or antibody-mediated approaches to assess the specific role of this lymphoid population in the induction of immune responses and adaptive immunity. The authors demonstrate a critical role for ILCs in the regulation of inflammatory adaptive immune responses to commensal bacteria that is independent of the effector cytokines IL-22, IL-17A and IL-23. In contrast to ILCs of groups 1 and 2, mouse and human RORγt+ ILCs express MHC class II and can process and present antigen. However, they lack expression of the costimulatory molecules CD40, CD80 and CD86 and inhibit the proliferation of CD4+ T cells through MHC class II–dependent interactions. Deletion of MHC class II on RORγt+ ILCs leads to commensal bacteria–driven pathological CD4+ T cell responses and intestinal inflammation.

Nature (22 May 2013) doi:10.1038/nature12240