IL-10-producing innate lymphoid cells restrain γδT17-driven psoriatic inflammation.

Psoriasis is a chronic inflammatory dermatosis driven by the interleukin (IL)-23-IL-17 axis, with γδ T cells as key IL-17A producers in lesional skin. IL-10 counter-regulates this pathway, and innate lymphoid cells (ILCs) are emerging tissue-resident immune regulators. Here we show that imiquimod (IMQ)-induced psoriatic inflammation elicits a programmed death-ligand 1 (PD-L1)hi stem cell antigen-1 (Sca-1)+ ILC2-like subset enriched for IL-10 (ILC210) that acts as an innate brake on the γδ T17 axis. Adoptive transfer of ILC210 reduced clinical severity and epidermal hyperplasia and suppressed γδ T cell IL-17A production and CCR2 expression in coculture; Il10 -/--derived ILC210 lacked these effects, indicating that IL-10 is required. Reanalysis of human psoriasis single-cell RNA sequencing datasets identified a PD-L1+IL-10+ ILC population in lesional skin. These findings define ILC210 as an IL-10-dependent innate regulatory checkpoint restraining γδ T17-driven psoriatic inflammation, revealing a previously unrecognized innate regulatory layer in this disease.