CD4+ T-cell-derived IL-10 promotes CNS inflammation in mice by sustaining effector T cell survival

Cell Rep. 2022 Mar 29;38(13):110565. doi: 10.1016/j.celrep.2022.110565.

Abstract

Interleukin (IL)-10 is considered a prototypical anti-inflammatory cytokine, significantly contributing to the maintenance and reestablishment of immune homeostasis. Accordingly, it has been shown in the intestine that IL-10 produced by Tregs can act on effector T cells, thereby limiting inflammation. Herein, we investigate whether this role also applies to IL-10 produced by T cells during central nervous system (CNS) inflammation. During neuroinflammation, both CNS-resident and -infiltrating cells produce IL-10; yet, as IL-10 has a pleotropic function, the exact contribution of the different cellular sources is not fully understood. We find that T-cell-derived IL-10, but not other relevant IL-10 sources, can promote inflammation in experimental autoimmune encephalomyelitis. Furthermore, in the CNS, T-cell-derived IL-10 acts on effector T cells, promoting their survival and thereby enhancing inflammation and CNS autoimmunity. Our data indicate a pro-inflammatory role of T-cell-derived IL-10 in the CNS.

Keywords: CP: Immunology; CP: Neuroscience; T cells; autoimmunity; cell death; experimental autoimmune encephalomyelitis, EAE; inflammation; interleukin-10.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes
  • Cell Survival
  • Central Nervous System
  • Inflammation
  • Interleukin-10* / physiology
  • Mice
  • T-Lymphocytes*

Substances

  • IL10 protein, mouse
  • Interleukin-10