STAT3 ablation in keratinocytes ameliorates allergic contact dermatitis in DNCB-induced mice model

Articles in Press

Document Type : Original Article

Authors

1 School of Public Health, North China University of Science and Technology, Tangshan, 063210, China

2 North China University of Science and Technology Affiliated Hospital, Tangshan, 063000, China

3 Department of Dermatology, the Second Affiliated Hospital of Xi ‘an Jiaotong University, Xi’an, 710004, China

10.22038/ijbms.2026.94064.20274

Abstract

Objective(s): Allergic contact dermatitis (ACD) is a T cell-mediated type IV hypersensitivity reaction to haptens. Its pathogenesis involves keratinocyte dysfunction and dysregulation of the Signal Transducer and Activator of Transcription 3 (STAT3)-signaling pathway. However, the specific role of keratinocyte produced STAT3 in ACD remains unclear. To investigate the effect of keratinocyte (KC)-specific STAT3 conditional knockout on 1-Chloro-2,4-dinitrobenzene (DNCB)-induced ACD in mice.
Materials and Methods: We generated keratinocyte-specific STAT3 conditional knockout (cKO) mice (K14-Cre⁺; STAT3flox/flox) and subjected them to DNCB-induced ACD, with STAT3flox/flox littermates as controls. Epidermal barrier function (transepidermal water loss and electrolyte permeability), histopathological inflammation (H&E and toluidine blue staining), and expression of inflammatory mediators (IL-1β, IL-6) were assessed. In vitro, STAT3 was knocked down by siRNA in HaCaT keratinocytes prior to stimulation with TNF-α/IFN-γ, followed by evaluation of inflammatory markers and STAT3 phosphorylation.
Results: Keratinocyte-specific STAT3 deletion significantly ameliorated ACD severity, evidenced by reduced TEWL values, enhanced epidermal barrier function, decreased dermatitis scores, reduced clinical dermatitis scores, decreased dermal inflammatory infiltration, lower spleen index, and attenuated mast cell degranulation. Molecular analysis revealed down-regulation of inflammation-related factors (IL-1β, IL-6, TNF-α, JAK2) and significant inhibition of STAT3 phosphorylation. In vitro, STAT3 knockdown significantly suppressed IL-1β, IL-6, JAK2, Caspase-3, and MMP-3 expression in HaCaT cells and reduced STAT3 phosphorylation.
Conclusion: Keratinocyte-specific STAT3 deletion alleviates epidermal barrier impairment and skin inflammation in ACD by inhibiting STAT3 phosphorylation and its downstream pro-inflammatory signaling.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 13 May 2026

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