Oncostatin M drives multifaceted immune pathogenesis in atopic dermatitis-like inflammation via neutrophil-dependent mechanisms

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by dysregulation of T helper 2 cell and accumulation of innate immune cells. While recent studies have highlighted the role of neutrophils in the onset and progression of AD, their precise contributions remain incompletely defined. In a mouse model of AD-like inflammation induced by calcipotriol and ovalbumin, neutrophils were identified as a major source of the cytokine oncostatin M (OSM). Neutrophil-derived OSM promoted broad immune cell recruitment, exacerbated skin inflammation, and enhanced the expression of neuronal markers associated with pruritus. Both the knockdown of OSM and neutrophil depletion attenuated inflammatory responses and neuronal activation. Publicly available single-cell RNA-sequencing datasets further confirmed increased OSM expression in neutrophils from lesional AD skin, underscoring the translational relevance of our findings. These results reveal a previously unrecognized intercellular communication axis in which neutrophil-derived OSM orchestrates multifaceted immune and neuroinflammatory responses in AD. Targeting this signaling pathway may offer a novel therapeutic avenue for AD and related inflammatory disorders.