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

Area of Science:

• Immunology
• Dermatology
• Innate Immunity

Background:

• Psoriasis is a chronic inflammatory skin disease.
• The interleukin-23/interleukin-17 (IL-23/IL-17) axis is central to psoriasis pathogenesis.
• Innate lymphoid cells (ILCs) are emerging regulators of tissue immunity.

Purpose of the Study:

• To investigate the role of ILCs in imiquimod (IMQ)-induced psoriatic inflammation.
• To identify specific ILC subsets involved in regulating the IL-23/IL-17 axis.
• To determine the function of IL-10-producing ILCs in psoriasis.

Main Methods:

• Induction of psoriatic inflammation in mice using imiquimod (IMQ).
• Characterization of ILC subsets, including programmed death-ligand 1 (PD-L1) and stem cell antigen-1 (Sca-1) expression.
• Adoptive transfer of ILC subsets and assessment of therapeutic effects.
• Analysis of γδ T cell activation markers (IL-17A and CCR2) in coculture.
• Reanalysis of human psoriasis single-cell RNA sequencing data.

Main Results:

• IMQ-induced psoriasis elicited a PD-L1^hiSca-1⁺ ILC2-like subset (ILC2₁₀) enriched for IL-10.
• Adoptive transfer of ILC2₁₀ ameliorated psoriatic inflammation and suppressed γδ T cell IL-17A production and CCR2 expression.
• IL-10 production by ILC2₁₀ was essential for its regulatory function.
• A PD-L1⁺IL-10⁺ ILC population was identified in human lesional psoriasis skin.

Conclusions:

• ILC2₁₀ cells act as an IL-10-dependent innate brake on γδ T17 cell-driven psoriatic inflammation.
• This study reveals a previously unrecognized innate regulatory mechanism in psoriasis.
• Targeting ILC2₁₀ may offer a novel therapeutic strategy for psoriasis.