Cinobufagin Directly Targets PDE4D to Disrupt Fibroblast-Dendritic Cell Crosstalk in Atopic Dermatitis.

ABSTRACT: Atopic dermatitis (AD) is a chronic inflammatory skin disease driven by immune dysregulation and Th2-dominant inflammation. This study identifies phosphodiesterase 4D (PDE4D) as a key regulator of AD pathogenesis and a potential therapeutic target. Single-cell RNA sequencing (scRNA-seq) revealed activation of the macrophage migration inhibitory factor (MIF) signaling pathway in lesional tissues, with inflammatory fibroblasts mediating MIF-driven interactions with myeloid cells. Elevated PDE4D expression in lesional tissues suppressed cyclic adenosine monophosphate (cAMP) signaling, promoting inflammation. Cinobufagin, a bufadienolide compound, is identified as a potent PDE4D inhibitor. Compared to other PDE4 inhibitors used in clinical cases, cinobufagin demonstrated superior efficacy in i

SUBMITTER: Li S 

PROVIDER: S-EPMC12752632 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature