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bioRxiv · 10.1101/2025.10.11.681540

Prolactin links psychological stress to psoriasis via a fibroblast-chemokine pathway

Ge, H.·Zhou, S.·Zhao, Y.·Zhang, X.·Chen, M.·Gao, P.·Liu, S.·Mu, Q.·Fang, D.·Hou, X.·Yong, L.
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Abstract

Psoriasis is a chronic inflammatory skin disease that forms a vicious cycle with psychological stress. Whether and how the hypothalamic-pituitary (HP) axis-mediated neuroendocrine system regulates psoriasis remains obscure. Here, we report elevated levels of the pituitary hormone prolactin (PRL) in both psoriasis patients and imiquimod (IMQ)-induced psoriasis mice. Mechanistically, PRL acts on dermal PRLR-expressing fibroblasts to promote the production of the chemokines CCL2 and CCL7, which then recruit monocytes/macrophages into psoriatic lesional skin, thereby activating local IL-17A-producing T cells. Accordingly, pharmacological targeting of PRL signaling inhibits the recruitment of monocytes/macrophages, decreases the frequency of IL-17A-producing T cells, and alleviates IMQ-induced psoriasis in mice. In summary, our results delineate a mechanism by which the neuroendocrine hormone PRL aggravates psoriasis and highlight a potential therapeutic strategy of inhibiting PRL-PRLR signaling, particularly in psoriasis patients experiencing psychological stress.

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Ge, H., Zhou, S., Zhao, Y., Zhang, X., Chen, M., Gao, P., Liu, S., Mu, Q., Fang, D., Hou, X., Yong, L.. 2025-10-13. Prolactin links psychological stress to psoriasis via a fibroblast-chemokine pathway. https://doi.org/10.1101/2025.10.11.681540

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