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

  • Author Footnotes
    4 These authors contributed equally to this work.
    Ke Xue
    Footnotes
    4 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, China

    State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi’an, China
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  • Author Footnotes
    4 These authors contributed equally to this work.
    Shuai Shao
    Footnotes
    4 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
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  • Hui Fang
    Affiliations
    Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
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  • Lirong Ma
    Affiliations
    College of Life Sciences, Northwest University, Xi’an, China
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  • Caixia Li
    Affiliations
    Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
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  • Author Footnotes
    5 These authors contributed equally to this work.
    Zifan Lu
    Footnotes
    5 These authors contributed equally to this work.
    Affiliations
    State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi’an, China
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  • Author Footnotes
    5 These authors contributed equally to this work.
    Gang Wang
    Correspondence
    Correspondence: Gang Wang, Department of Dermatology, Xijing Hospital, Fourth Military Medical University, 127 Changlexi Road, Xi’an 710032, China.
    Footnotes
    5 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
    Search for articles by this author
  • Author Footnotes
    4 These authors contributed equally to this work.
    5 These authors contributed equally to this work.
Published:October 20, 2021DOI:https://doi.org/10.1016/j.jid.2021.09.027
      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.

      Abbreviations:

      CVD (cardiovascular disease), Ex-4 (exendin-4), HFD (high-fat diet), IMQ (imiquimod), KC (keratinocyte), MetS (metabolic syndrome), MI (myocardial infarction), ND (normal diet), NHK (normal human keratinocyte), p-STAT3 (phosphorylated signal transducer and activator of transcription 3), pso-mix (psoriasis mix), PV (psoriasis vulgaris), STAT3 (signal transducer and activator of transcription 3), Th (T helper type)
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