2. Academic Validation
  3. Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice

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

  • Nat Commun. 2022 Jul 22;13(1):4255. doi: 10.1038/s41467-022-31935-8.
Liang Yong  # 1 2 3 4 5,  Yafen Yu  # 1 2 3 4 5,  Bao Li  # 6,  Huiyao Ge 1 2 3 4 5,  Qi Zhen 1 2 3 4 5,  Yiwen Mao 1 2 3 4 5,  Yanxia Yu 1 2 3 4 5,  Lu Cao 1 2 3 4 5,  Ruixue Zhang 1 2 3 4 5,  Zhuo Li 1 2 3 4 5,  Yirui Wang 1 2 3 4 5,  Wencheng Fan 1 2 3 4 5,  Chang Zhang 1 2 3 4 5,  Daiyue Wang 1 2 3 4 5,  Sihan Luo 1 2 3 4 5,  Yuanming Bai 1 2 3 4 5,  Shirui Chen 1 2 3 4 5,  Weiwei Chen 1 2 3 4 5,  Miao Liu 7,  Jijia Shen 7,  Liangdan Sun 8 9 10 11 12
Affiliations

Affiliations

  • 1 Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 2 Institute of Dermatology, Anhui Medical University, Hefei, China.
  • 3 Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China.
  • 4 Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China.
  • 5 Anhui Provincial Institute of Translational Medicine, Hefei, China.
  • 6 Integrated Laboratory, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
  • 7 Anhui Provincial Laboratory of Microbiology and Parasitology; Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China.
  • 8 Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, China. ahmusld@163.com.
  • 9 Institute of Dermatology, Anhui Medical University, Hefei, China. ahmusld@163.com.
  • 10 Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China. ahmusld@163.com.
  • 11 Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China. ahmusld@163.com.
  • 12 Anhui Provincial Institute of Translational Medicine, Hefei, China. ahmusld@163.com.
  • # Contributed equally.
PMID: 35869084 DOI: 10.1038/s41467-022-31935-8
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.

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