2. Academic Validation
  3. Stress aggravates imiquimod-induced psoriasiform inflammation by promoting M1 macrophage polarization

Stress aggravates imiquimod-induced psoriasiform inflammation by promoting M1 macrophage polarization

  • Int Immunopharmacol. 2023 Sep 7;124(Pt A):110899. doi: 10.1016/j.intimp.2023.110899.
Huiyao Ge 1,  Yiwen Mao 1,  Weiwei Chen 1,  Zhuo Li 1,  Yanxia Yu 1,  Sihan Luo 1,  Daiyue Wang 1,  Yuanming Bai 1,  Wencheng Fan 1,  Yirui Wang 1,  Qi Zhen 2,  Liangdan Sun 3
Affiliations

Affiliations

  • 1 Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China.
  • 2 North China University of Science and Technology Affiliated Hospital, Tangshan, China; Inflammation and Immune Diseases Laboratory of North China University of Science and Technology, Tangshan, China; School of Public Health, North China University of Science and Technology, Tangshan, China. Electronic address: ahmedzq@163.com.
  • 3 Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China; Health Science Center, North China University of Science and Technology, Tangshan, China; North China University of Science and Technology Affiliated Hospital, Tangshan, China; Inflammation and Immune Diseases Laboratory of North China University of Science and Technology, Tangshan, China. Electronic address: ahmusld@163.com.
PMID: 37688915 DOI: 10.1016/j.intimp.2023.110899
Abstract

Psychological stress has long been considered to cause the aggravation and recurrence of psoriasis, but the underlying mechanism remains largely unknown. Here, we used a mouse model of restraint-induced stress and imiquimod (IMQ)-induced psoriasiform inflammation to investigate the crosstalk between stress and the skin immune system and their functions in the pathogenesis of psoriasis. We found that stress aggravated skin inflammation and elevated serum corticosterone (CORT) levels in mice. Stress also increased the number of macrophages and Glucocorticoid Receptor (GR) expression in IMQ-treated mouse skin. GR agonist CORT upregulated the phosphorylation of STAT1 to promote M1 macrophage polarization in vitro. Additionally, GR deletion in macrophages and pharmacologic inhibition of GR improved skin inflammation and reduced M1 macrophage polarization under stress. Taken together, these results indicate that stress aggravates psoriasiform inflammation by promoting CORT/GR signaling-induced M1 macrophage polarization, suggesting that blocking the GR signaling has great potential as an Adjuvant treatment for psoriasis patients with chronic stress.

Keywords

Glucocorticoid receptor; Macrophage polarization; Psoriasiform inflammation; Psychological stress.

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