CD 1d‐mediated activation of group 3 innate lymphoid cells drives IL ‐22 production

Innate lymphoid cells ( ILC s) are a heterogeneous family of immune cells that play a critical role in a variety of immune processes including host defence against infection, wound healing and tissue repair. Whether these cells are involved in lipid‐dependent immunity remains unexplored. Here we show that murine ILC s from a variety of tissues express the lipid‐presenting molecule CD 1d, with group 3 ILC s ( ILC 3s) showing the highest level of expression. Within the ILC 3 family, natural cytotoxicity triggering receptor ( NCR ) − CCR 6 + cells displayed the highest levels of CD 1d. Expression of CD 1d on ILC s is functionally relevant as ILC 3s can acquire lipids in vitro and in vivo and load lipids on CD 1d to mediate presentation to the T‐cell receptor of invariant natural killer T ( iNKT ) cells. Conversely, engagement of CD 1d in vitro and administration of lipid antigen in vivo induce ILC 3 activation and production of IL ‐22. Taken together, our data expose a previously unappreciated role for ILC s in CD 1d‐mediated immunity, which can modulate tissue homeostasis and inflammatory responses.