PD-1 regulates KLRG1⁺ group 2 innate lymphoid cells

Group 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens and maintain tissue homeostasis in response to cytokines. Positive regulation of ILC-2s through ICOS has been recently elucidated. We demonstrate here that PD-1 is an important negative regulator of KLRG1⁺ ILC-2 function in both mice and humans. Increase in KLRG1⁺ ILC-2 cell numbers was attributed to an intrinsic defect in PD-1 signaling, which resulted in enhanced STAT5 activation. During Nippostrongylus brasiliensis infection, a significant expansion of KLRG1⁺ ILC-2 subsets occurred in Pdcd1^-/- mice and, upon adoptive transfer, Pdcd1^-/- KLRG1⁺ ILC-2s significantly reduced worm burden. Furthermore, blocking PD-1 with an antibody increased KLRG1⁺ ILC-2 cell number and reduced disease burden. Therefore, PD-1 is required for maintaining the number, and hence function, of KLRG1⁺ ILC-2s.