IL-37 suppresses CNS autoimmunity by increasing the frequency of Treg cells and reducing CD4 + T cell-derived IL-10 production

J Neuroinflammation. 2024 Nov 19;21(1):301. doi: 10.1186/s12974-024-03295-1.

Abstract

Background: Interleukin-37 (IL-37) has anti-inflammatory properties in innate and adaptive immunity. Patients with multiple sclerosis (MS), an autoimmune inflammatory demyelinating disease of the central nervous system (CNS), have increased serum levels of IL-37. However, it is unknown whether IL-37 has an inhibitory effect on ongoing autoimmune neuroinflammation, thus offering a potential MS therapy.

Aim: Here, we examined the effect of IL-37 in an experimental autoimmune encephalomyelitis (EAE) model after disease onset to determine if it was protective.

Findings: IL-37-treated mice developed a less severe disease than control mice, with reduced demyelination as determined by increased expression of myelin basic protein. IL-37 suppressed inflammation by decreasing infiltration of CD4 + T cells into the CNS and increasing the frequency of regulatory T cells, while IL-10 expression by CD4 + T cells decreased over time in the CNS.

Conclusion: Our findings confirm the immunomodulatory role of IL-37 in CNS inflammation during ongoing disease, thus indicating the potential of IL-37 as an inhibitory reagent for MS therapy.

Keywords: Experimental autoimmune encephalomyelitis (EAE); IL-10; IL-37; Inflammation; Multiple sclerosis.

MeSH terms

  • Animals
  • Autoimmunity / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Central Nervous System / immunology
  • Central Nervous System / metabolism
  • Encephalomyelitis, Autoimmune, Experimental* / immunology
  • Encephalomyelitis, Autoimmune, Experimental* / metabolism
  • Female
  • Interleukin-1* / metabolism
  • Interleukin-10* / metabolism
  • Mice
  • Mice, Inbred C57BL*
  • T-Lymphocytes, Regulatory* / drug effects
  • T-Lymphocytes, Regulatory* / immunology
  • T-Lymphocytes, Regulatory* / metabolism

Substances

  • Interleukin-1
  • Interleukin-10
  • IL37 protein, human