Work

Macrophagic Ym1 orchestrates γδT cell-derived IL-17 production and keratinocyte functionality to mediate psoriasis-like skin inflammation

Year: 2025

Type: article

Abstract: Psoriasis is a chronic inflammatory skin disease, with the IL-17 pathway being a key contributor. Ym1, a positionally cloned inflammation regulatory gene linked to various disorders, has an unclear effect on skin inflammation. In this study, the role of Ym1 was investigated in both mannan and imiquimod-induced psoriasis-like dermatitis models, using Ym1-deficient congenic mice. Natural polymorphism of Ym1 influenced the development of skin inflammation, dependent on macrophages, since adoptive transferring of Ym1-deficient macrophages alleviated disease, whereas recombinant Ym1 worsened it. Particularly, Ym1 congenic mice exhibited decreased IL-17 production in innate immune cells, and depletion of γδT cells mitigated disease and lowered skin IL-17 levels. Additionally, RNA-seq analysis revealed Ym1-regulated keratinization in lesional skin. Recombination Ym1 directly influenced the inflammatory response and proliferation of mouse primary keratinocytes. Collectively, we conclude that Ym1 regulates γδT cell-derived IL-17 production and keratinocyte functionality, and thereby contributes to skin inflammation in mice.

Source: Communications Biology

DOI: 10.1038/s42003-025-08628-1