Increased CRHR1 expression on monocytes from patients with AA enables a pro-inflammatory response to corticotrophin-releasing hormone

Exp Dermatol. 2024 Oct;33(10):e15182. doi: 10.1111/exd.15182.

Abstract

Stress may play a key role in alopecia areata (AA), though the exact interactions of stress with AA remain undefined. Corticotropin-releasing hormone (CRH), the proximal regulator of the stress axis, has been recognized as an immunomodulatory factor in tissues and peripheral blood mononuclear cells (PBMCs). We used multicolour flow cytometry to identify receptor CRHR1 expression on PBMC subsets in AA patients (n = 54) and controls (n = 66). We found that CRHR1 was primarily expressed by circulating monocytes. CRHR1 expression on monocytes was enhanced in AA compared with controls (3.17% vs. 1.44%, p = 0.002, chi-squared test). AA incidence was correlated to elevated CD14+ monocyte numbers (R = 0.092, p = 0.036) and markedly independently correlated with increased CRHR1 expression (R = 0.215, p = 0.027). High CRHR1 expression was significantly related to chronic AA (disease duration >1 year; p = 0.003, chi-squared test), and large lesion area (AA area >25%; p = 0.049, chi-squared test). We also observed enhanced percentages of active monocytes and reduced CD16+ CD3- NK cell numbers in AA patients' PBMCs (p = 0.010; 0.025, respectively). In vitro CRH treatment of PBMCs and human monocyte cell line THP-1 promoted CD86 upregulation. The findings imply that stress-related factors CRH and CRHR1 contribute to AA development and progression where higher CRHR1 expression is associated with chronic AA and larger lesions.

Keywords: CRHR1; alopecia areata; corticotropin‐releasing hormone; peripheral blood mononuclear cells; stress.

Publication types

  • Letter

MeSH terms

  • Adult
  • Alopecia Areata* / metabolism
  • Case-Control Studies
  • Corticotropin-Releasing Hormone* / metabolism
  • Female
  • Flow Cytometry
  • Humans
  • Killer Cells, Natural / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Male
  • Middle Aged
  • Monocytes* / metabolism
  • Receptors, Corticotropin-Releasing Hormone* / metabolism
  • Receptors, IgG / metabolism
  • Young Adult

Substances

  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1
  • Corticotropin-Releasing Hormone
  • Lipopolysaccharide Receptors
  • Receptors, IgG