Elevated IL-23 in skin promotes IL-23 derived Th17 responses in leprosy patients

Clin Exp Pharmacol Physiol. 2022 Sep;49(9):1002-1009. doi: 10.1111/1440-1681.13689. Epub 2022 Jul 4.

Abstract

Leprosy is an infectious disease caused by non-cultivable bacteria Mycobacterium leprae. Th17 cells play vital roles during pathogenesis of leprosy reactions and IL-23 is involved in Th17 cell differentiation. Although previous studies have reported the participation of IL-23 in leprosy patients in peripheral blood, the role of this cytokine in skin has not yet been described for the disease. In this study, we first evaluated IL-23 expression in the skin of patients with leprosy. Data showed that in keratinocytes, endothelial cells, and macrophages, IL-23 expression was markedly higher in patients compared to that in the normal skin controls. Also, leprosy patients presented higher percentage of IL-17A-producing IL-23R + CD4 T cells than healthy donors. IL-23R blocking induced markedly downregulated IL-17A secretion in leprosy patients but not in healthy donors. Furthermore, TGF-β expression was significantly elevated after IL-23R blocking. Overall, this study establishes that Th17 cells produce IL-17A in an IL-23 dependent manner in the skin of leprosy patients and provides more focused treatment strategies for Mycobacterium leprae.

Keywords: IL-23; Th17 cells; leprosy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endothelial Cells / metabolism
  • Humans
  • Interleukin-17 / metabolism
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Leprosy* / microbiology
  • Leprosy* / pathology
  • Mycobacterium leprae / metabolism
  • Th17 Cells* / metabolism

Substances

  • IL23A protein, human
  • Interleukin-17
  • Interleukin-23
  • Interleukin-23 Subunit p19