Human YKL-40 antibody alleviates atopic dermatitis-like skin inflammation by inhibiting exosome secretion via the JAK3/STAT6 pathway.

Abstract

Atopic dermatitis (AD) is an inflammatory skin disease that produces a variety of inflammatory cytokines and chemokines. Chitinase-3-like protein 1 (CHI3L1, YKL-40) significantly contributes to AD-associated inflammatory response and is highly expressed in patients with AD. Therefore, this study elucidated the effects and potential mechanisms of human YKL-40 antibody on AD-affected skin. The anti-AD like inflammatory effects and inhibition of exosome release effectors of human YKL-40 antibody were evaluated. Since exosomes have been closely related to AD inflammation and cytokine production, we detected exosome release in in vitro reconstituted human skin (RHS) models and HaCaT cells. Cytokine expression was analyzed using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, related signaling pathways were evaluated using Western blotting and immunofluorescence staining. Human YKL-40 antibody significantly inhibited epidermal hyperplasia commonly induced by AD in the RHS model. In addition, this antibody effectively reduced the secretion of AD-associated inflammatory cytokines. Furthermore, it inhibited the expression of CD63, a marker for exosomes, and the phosphorylation of JAK3/STAT6, which are primarily involved in signaling pathways for AD and exosome release. This study provides strong evidence supporting the potential therapeutic efficacy of human YKL-40 antibody in the treatment of AD. It offers a new therapeutic approach for patients with incurable inflammatory skin diseases.