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Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice

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  • Liang Yong

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Yafen Yu

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Bao Li

    (Anhui Medical University)

  • Huiyao Ge

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Qi Zhen

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Yiwen Mao

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Yanxia Yu

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Lu Cao

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Ruixue Zhang

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Zhuo Li

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Yirui Wang

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Wencheng Fan

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Chang Zhang

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Daiyue Wang

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Sihan Luo

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Yuanming Bai

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Shirui Chen

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Weiwei Chen

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

  • Miao Liu

    (Anhui Medical University)

  • Jijia Shen

    (Anhui Medical University)

  • Liangdan Sun

    (the First Affiliated Hospital of Anhui Medical University
    Anhui Medical University
    Ministry of Education
    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province)

Abstract

CaMK4 has an important function in autoimmune diseases, and the contribution of CaMK4 in psoriasis remains obscure. Here, we show that CaMK4 expression is significantly increased in psoriatic lesional skin from psoriasis patients compared to healthy human skin as well as inflamed skin from an imiquimod (IMQ)-induced mouse model of psoriasis compared to healthy mouse skin. Camk4-deficient (Camk4−/−) mice treated with IMQ exhibit reduced severity of psoriasis compared to wild-type (WT) mice. There are more macrophages and fewer IL-17A+γδ TCR+ cells in the skin of IMQ-treated Camk4−/− mice compared to IMQ-treated WT mice. CaMK4 inhibits IL-10 production by macrophages, thus allowing excessive psoriatic inflammation. Deletion of Camk4 in macrophages alleviates IMQ-induced psoriatic inflammation in mice. In keratinocytes, CaMK4 inhibits apoptosis as well as promotes cell proliferation and the expression of pro-inflammatory genes such as S100A8 and CAMP. Taken together, these data indicate that CaMK4 regulates IMQ-induced psoriasis by sustaining inflammation and provides a potential target for psoriasis treatment.

Suggested Citation

  • Liang Yong & Yafen Yu & Bao Li & Huiyao Ge & Qi Zhen & Yiwen Mao & Yanxia Yu & Lu Cao & Ruixue Zhang & Zhuo Li & Yirui Wang & Wencheng Fan & Chang Zhang & Daiyue Wang & Sihan Luo & Yuanming Bai & Shir, 2022. "Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31935-8
    DOI: 10.1038/s41467-022-31935-8
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    3. Ferzin Sethna & Wei Feng & Qi Ding & Alfred J. Robison & Yue Feng & Hongbing Wang, 2017. "Enhanced expression of ADCY1 underlies aberrant neuronal signalling and behaviour in a syndromic autism model," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
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