Long-mu-pi-yan-fang ameliorates atopic dermatitis-like skin inflammation by modulating interleukin-22 receptor-mediated inflammatory signaling.

BACKGROUND

Long-mu-pi-yan-fang (LMPYF) has been used in clinical practice for the management of atopic dermatitis (AD), yet its underlying mechanisms remain unclear.

PURPOSE: To investigate the potential mechanisms of LMPYF in the treatment of AD.

METHODS

The therapeutic effects of LMPYF at different doses were evaluated in 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mice. RNA sequencing (RNA-seq) and molecular dynamics simulations were performed to explore potential therapeutic targets. The clinical relevance of the identified target was assessed in skin specimens from AD patients by analyzing its correlation with disease severity, and the associated mechanisms were further examined through in vitro experiments.

RESULTS

LMPYF ameliorated DNCB-induced AD-like lesions and epidermal hyperplasia, accompanied by reduced immunoglobulin E and T helper 2 cytokines. RNA-seq and molecular dynamics simulations suggested interleukin-22 receptor subunit α 1 (IL22RA1) as a potential LMPYF-associated target, with selected LMPYF constituents exhibiting stable interactions with IL22RA1. In clinical samples, IL22RA1 expression was elevated in lesional skin from AD patients and was positively correlated with disease severity. Further experimental validation showed that LMPYF reduced IL22RA1 expression and suppressed the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) signaling axis in vitro, which was consistent with reduced STAT3 phosphorylation in vivo. Furthermore, IL22RA1 knockdown in HaCaT cells stimulated with IL-4, IL-13, and tumor necrosis factor (TNF)-α attenuated the anti-inflammatory effects of LMPYF, suggesting that IL22RA1 may contribute to the cellular response to LMPYF.

CONCLUSION

This study suggests that LMPYF may ameliorate AD-like skin inflammation, at least in part, by modulating the IL22RA1/JAK1/STAT3 axis.