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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE290386 | GEO | 2026/01/06

REPOSITORIES: GEO

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Project description:Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous lesions and intense pruritus. Skin inflammation mediated by transient receptor potential vanillin 3 (TRPV3) in keratinocytes is a key mechanism driving the progression of AD. Paeonol is a bioactive phenolic compound extracted from the root bark of the Paeonia genus, which has demonstrated anti-inflammatory activities. Whether paeonol alleviates skin inflammation by inhibiting TRPV3 in the treatment of AD remains unclear.Objective: This study aims to investigate the therapeutic efficacy of paeonol against AD and its underlying anti-inflammatory mechanism.Methods: The therapeutic effects of paeonol were evaluated in a mouse model of AD induced by MC903 or carvacrol, as well as in tumor necrosis factor-alpha (TNF-α)-stimulated HaCaT cell line. Itch-related behaviors, hematoxylin-eosin (H&E) staining and toluidine blue staining were assessed in AD mice to evaluate the anti-atopic activity of paeonol. TRPV3 expression and function in keratinocytes were examined by Quantitative Real-time-PCR (qPCR), WB, immunofluorescence (IF) and Ca2+ imaging experiments. The anti-inflammation effect and its mechanisms of paeonol were measured by RNA sequencing (RNA-seq), H&E staining, qPCR and ELISA. Whole-cell patch-clamp were used to measure the excitability of trigeminal ganglion (TG) neurons treated by Chemokine (C-C motif) ligand 3 (CCL3).Results: Paeonol significantly alleviated MC903 and carvacrol-induced pruritus, epidermal hyperplasia and skin inflammation. Paeonol inhibited the expression and function of TRPV3 in keratinocytes, thereby inhibiting the activating of nuclear factor κB (NF-κB) pathway and reducing the secretion of CCL3. Downregulation of CCL3 expression in keratinocytes reduces the number of macrophages in the skin and inhibits their polarization to the M1 type. Moreover, paeonol also reversed the hyperexcitability of TG induced by increased CCL3, thus alleviated pruritus. Conclusion: Our study demonstrated that the activation of TRPV3 in keratinocytes aggravated skin inflammation and pruritus by promoting the secretion of CCL3. Paeonol alleviated AD by inhibiting the TRPV3/NF-κB/CCL3 axis in keratinocytes, thereby reducing macrophage-related skin inflammation, and inhibiting the hyperexcitability of TG neurons. These findings provide a novel therapeutic mechanism of paeonol in treating AD.

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

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