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Serotonin 2A receptor attenuates psoriatic inflammation by suppressing IL-23 secretion in monocyte-derived Langerhans cells

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Listed:
  • Yeh Fong Tan

    (National Yang Ming Chiao Tung University and Academia Sinica
    Academia Sinica)

  • Chen-Yun Yeh

    (Academia Sinica)

  • Sheng-Yun Hsu

    (Academia Sinica
    National Defense Medical Center)

  • Chun-Hao Lu

    (Academia Sinica)

  • Ching-Hui Tsai

    (Academia Sinica)

  • Pei-Chuan Chiang

    (Academia Sinica)

  • Hao-Jui Weng

    (Taipei Medical University-Shuang Ho Hospital
    Taipei Medical University)

  • Tsen-Fang Tsai

    (National Taiwan University Hospital)

  • Yungling Leo Lee

    (Academia Sinica
    China Medical University)

Abstract

Anecdotal evidence has suggested an association between psychiatric drugs and psoriasis, but consensus is absent due to contradicting reports, and the mechanism remains poorly defined. Here, we investigate the function of serotonin 2A receptor (HTR2A), a receptor commonly targeted by psychiatric drugs, in regulating psoriasis. HTR2A antagonistic drugs worsen psoriatic outcome, and HTR2A modulation reduces psoriatic inflammation. Using the Imiquimod-induced psoriasiform model, HTR2A-deficient mice manifest exacerbated inflammation. Hematopoietic cells, particularly monocyte-derived Langerhans cells (moLC), are involved in this phenotype. Mechanistically, the exacerbated inflammation is due to increased interleukin-23 (IL-23) secretion, and HTR2A suppresses this by inhibiting activation of the non-canonical NFκB pathway. Serotonin is the putative agonist modulating HTR2A, attenuating psoriatic inflammation. Lastly, our findings in mice are also validated clinically. Our data demonstrate that serotonin modulates HTR2A, attenuating psoriatic inflammation by suppressing IL-23 secretion via inhibiting the non-canonical NFκB pathway in moLCs.

Suggested Citation

  • Yeh Fong Tan & Chen-Yun Yeh & Sheng-Yun Hsu & Chun-Hao Lu & Ching-Hui Tsai & Pei-Chuan Chiang & Hao-Jui Weng & Tsen-Fang Tsai & Yungling Leo Lee, 2025. "Serotonin 2A receptor attenuates psoriatic inflammation by suppressing IL-23 secretion in monocyte-derived Langerhans cells," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63971-5
    DOI: 10.1038/s41467-025-63971-5
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