Dermal fibroblasts respond to interleukin-4 and 13 and promote T-cell recruitment in atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by type 2 immune responses. While immune cells and keratinocytes are established contributors to AD pathogenesis, the role of dermal fibroblasts remains less defined. Here, we investigated whether fibroblasts contribute to T cell recruitment by producing chemokines in response to type 2 cytokines. Single-cell RNA sequencing (scRNA-seq) of human AD skin and murine models, including IL-4 receptor-deficient mice, revealed transcriptionally distinct fibroblast clusters, with IL-4Ra-dependent populations expressing high levels of chemokines. In vitro, IL-4/IL-13 synergized with inflammatory cytokines(Inf; TNFa + IL-17A + IL-1b) to induce fibroblast expression of CCR3 ligands, including Ccl8. Conditioned media from stimulated fibroblasts promoted T cell migration in a CCR3-dependent manner. Furthermore, pharmacologic inhibition of CCR3 reduced T cell infiltration and skin inflammation in two AD mouse models. These findings demonstrate that dermal fibroblasts are not passive structural cells but active participants in type 2 inflammation, contributing to the pathogenesis of AD by producing chemokines that facilitate T cell recruitment. Targeting the fibroblast–CCR3 axis may represent a novel therapeutic strategy for AD. Overall design: Bulk RNA-seq of fibroblasts stimulated in vitro