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 T helper 2 cell dysregulation and accumulation of innate immune cells. While recent studies have highlighted a role for 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. Knockdown of OSM and neutrophil depletion both 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. Overall design: Mice ears were treated with calcipotriol and ovalbumin to induce AD-like inflammation. Immune responses were assessed through histological examination and quantitative PCR. RNA sequencing was conducted for unbiased transcriptomic analysis of skin lesions. To investigate the role of selected inflammatory mediators, small interfering RNA (siRNA) and neutralizing antibodies were employed in cell lines and mouse models, respectively.