Elevated RIPK2 Expression in Atopic Dermatitis Skin Is Associated with Mixed Th1/Th2 Cytokine Responses in CD4+ T Cells

Receptor-interacting protein kinase 2 (RIPK2) is a critical mediator of the immune system leading to production of pro-inflammatory cytokines. Its role in the pathogenesis of atopic dermatitis (AD) has not been defined. This work aims to assess RIPK2 expression in the skin in AD and to evaluate the association with Th1-, Th2-, and Th17-related cytokine expression in lesional skin. AD patients’ skin biopsies and healthy controls were collected. An OPAL multiplex immunohistochemistry method was used to simultaneously detect TNF-α, IL-4, IL-13 and IL-17 in CD4+ RIPK2+ and CD4+ RIPK2− T cells. Quantitative image analysis was performed, and group comparisons were made using non-parametric Mann–Whitney tests. Our results show that CD4+RIPK2+ cells were significantly abundant in AD skin, with mark increased expression of Th1, Th2, and Th17 cytokines simultaneously. However, CD4+ RIPK2− T cells in AD overexpress TNFa without elevated Th2 cytokines, and IL-17+ cells were only marginally increased. In conclusion RIPK2 expression is upregulated in infiltrating CD4+ T cells in AD skin, with a mixed Th1/Th2 cytokine profile, suggesting that enhanced RIPK2 signaling contributes to the immune dysregulation in adult AD. These findings identify RIPK2 as a potential marker of Th1/Th2-high immune endotypes in AD and as a possible therapeutic target for intervention.