Adipocyte-Derived CTRP3 Exhibits Anti-Inflammatory Effects via LAMP1-STAT3 Axis in Psoriasis.

Abstract

Psoriasis is a systemic disease that is associated with metabolic disorders, which may contribute to abnormal adipokine levels. However, the underlying mechanism is largely unknown. Here, we investigated the role of the adipokine CTRP3 in the pathogenesis of psoriasis and comorbidities. The circulating CTRP3 level in patients with psoriasis was significantly lower than that in healthy controls and negatively correlated with metabolic risk factors. Rescuing CTRP3 levels with the GLP-1 receptor agonist exendin-4 in diet-induced obese mice could alleviate its more severe psoriatic symptoms in an imiquimod-induced mouse model. Topical application of CTRP3 also exerted a protective effect on imiquimod-induced normal diet mice. Moreover, CTRP3 could directly inhibit the inflammatory responses of psoriatic keratinocytes by blocking phosphorylation of signal transducer and activator of transcription 3 via LAMP1 in vitro. We identified the critical psoriatic cytokines, including IL-17A and TNF-α, that impaired adipocyte differentiation and sufficient CTRP3 secretion. In sum, our study reveals that adipocyte dysfunction and low level of CTRP3 caused by IL-17A exacerbates psoriasis progression and related metabolic syndrome, implying a mechanism underlying the vicious cycle between psoriasis and metabolic disorders. Pharmacological agents that improve CTRP3 level in obese patients with psoriasis may be considered as a potential strategy for psoriasis treatment.

• Authors: Ke Xue, Shuai Shao, Hui Fang, Lirong Ma, Caixia Li, Zifan Lu, Gang Wang
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 142 Issue 5 Pg. 1349-1359.e8 (05 2022) ISSN: 1523-1747 [Electronic] United States
• PMID: 34687744 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Adipokines
• Anti-Inflammatory Agents
• CORS26 protein, mouse
• Interleukin-17
• LAMP1 protein, human
• Lysosomal Membrane Proteins
• STAT3 Transcription Factor
• STAT3 protein, human
• Imiquimod

Topics

• Adipocytes (metabolism)
• Adipokines (metabolism)
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Disease Models, Animal
• Humans
• Imiquimod (pharmacology)
• Interleukin-17 (metabolism)
• Keratinocytes (metabolism)
• Lysosomal Membrane Proteins (metabolism)
• Mice
• Psoriasis (pathology)
• STAT3 Transcription Factor (metabolism)