Antigen-independent IL-17A production by bystander-activated CD4+IL-1R1+ cells in patients with multiple sclerosis

Hum Immunol. 2023 Mar;84(3):241-246. doi: 10.1016/j.humimm.2022.12.004. Epub 2023 Jan 4.

Abstract

Multiple sclerosis (MS) is a demyelinating disease caused by auto-antigen recognizing CD4+ T cells. However, IL-17A-producing CD4+ T cells that are bystander-activated by IL-1β and IL-23, and T cell receptors independently, could contribute to experimental autoimmune encephalomyelitis. Here, we studied the differences in the frequency and function of bystander-activated CD4+ T cells in patients with MS. A significantly higher frequency of CD4 + IL-1Rl + T cells was found in memory than in naïve CD4+ T cells and in Th17/Th17.1 than in Th1/Th2 subtypes in both MS and healthy controls (HC). Following IL-1β and IL-23 stimulation, IL-1Rl expression was markedly increased in both memory and Th17/Th17.1 cells, and their IL-17A-production was increased after bystander-activation, which was significantly higher in MS compared with HC. Our study suggests a potential role of IL-17A-producing bystander-activated CD4+IL-1Rl+ T cells in MS.

Keywords: Bystander-activation; IL-17A; Multiple sclerosis.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes*
  • Encephalomyelitis, Autoimmune, Experimental
  • Humans
  • Interleukin-17* / metabolism
  • Interleukin-23 / metabolism
  • Multiple Sclerosis* / metabolism
  • Th17 Cells

Substances

  • Interleukin-17
  • Interleukin-23