Academia Sinica Logo

Psoriasis is a chronic IL-23/IL-17–related immune disorder characterized by erythematous plaques, silvery scales, and psychological burden. Symptom changes after psychiatric drug use suggest additional mechanisms are involved. The team of Dr. Yungling Leo Lee identified serotonin 2A receptor (HTR2A) expression on skin Langerhans cells (LCs). Their study revealed that monocyte-derived LCs (moLCs) are key regulators of psoriasis severity; activation of HTR2A with an agonist reduced IL-23 secretion, leading to decreased Vγ4+ γδT cells producing IL-17 and IL-22. Mechanistically, HTR2A activation inhibited generation of the p52 subunit in the noncanonical NFκB pathway, thereby suppressing IL-23 expression. Analysis of patient skin and blood samples further showed lower HTR2A expression on moLCs and reduced platelet serotonin compared with healthy controls. These findings uncover a link between HTR2A and psoriasis, providing new insights for future therapeutic development.

This study was supported by Academia Sinica and National Taiwan University Hospital, and conducted by the joint team from Dr. Yungliang Leo Lee at Institute of Biomedical Sciences and Dr. Tsen-Fang Tsai at National Taiwan University Hospital. Clinical samples were collected by National Taiwan University Hospital and Shuang Ho Hospital, data analysis was supported by the Taiwan National Health Insurance Research Database, and services were provided by the NTU Transgenic Mouse Models Core Facility. The study was published on September 29, 2025 in Nature Communications.