Unveiling multifaceted roles of myeloid innate immune cells in the pathogenesis of psoriasis

Abstract

Psoriasis is a chronic inflammatory skin disease occurring worldwide. Initially viewed as a keratinocyte disorder, psoriasis is now recognized to involve a complex interplay between genetic predisposition, environmental triggers, and a dysregulated immune system, with a significant role of CD4⁺ T cells producing IL-17. Recent genetic studies have identified susceptibility loci that underscore the importance of innate immune responses, particularly the roles of myeloid cells, such as dendritic cells, macrophages, and neutrophils. These cells initiate and sustain inflammation through cytokine production triggered by external stimuli. They influence keratinocyte behavior and interact with adaptive immune cells. Recent techniques have further revealed the heterogeneity of myeloid cells in psoriatic lesions, highlighting the contributions of less-studied subsets, such as eosinophils and mast cells. This review examines the multifaceted roles of myeloid innate immune cells in psoriasis, emphasizing their functional diversity in promoting psoriatic inflammation. It also describes current treatment targeting myeloid innate immune cells and explores potential new therapeutic strategies based on the functional characteristics of these subsets. Future research should focus on the detailed characterization of myeloid subsets and their interactions to develop targeted treatments that address the complex immune landscape of psoriasis.