CD4 + Th2 cells are directly regulated by IL-10 during allergic airway inflammation

Mucosal Immunol. 2017 Jan;10(1):150-161. doi: 10.1038/mi.2016.47. Epub 2016 May 11.

Abstract

Interleukin-10 (IL-10) is an important regulatory cytokine required to control allergy and asthma. IL-10-mediated regulation of T cell-mediated responses was previously thought to occur indirectly via antigen-presenting cells. However, IL-10 can act directly on regulatory T cells and T helper type 17 (Th17) cells. In the context of allergy, it is therefore unclear whether IL-10 can directly regulate T helper type 2 (Th2) cells and whether this is an important regulatory axis during allergic responses. We sought to determine whether IL-10 signaling in CD4+ Th2 cells was an important mechanism of immune regulation during airway allergy. We demonstrate that IL-10 directly limits Th2 cell differentiation and survival in vitro and in vivo. Ablation of IL-10 signaling in Th2 cells led to enhanced Th2 cell survival and exacerbated pulmonary inflammation in a murine model of house dust mite allergy. Mechanistically, IL-10R signaling regulated the expression of several genes in Th2 cells, including granzyme B. Indeed, IL-10 increased granzyme B expression in Th2 cells and led to increased Th2 cell death, identifying an IL-10-regulated granzyme B axis in Th2 cells controlling Th2 cell survival. This study provides clear evidence that IL-10 exerts direct effects on Th2 cells, regulating the survival of Th2 cells and severity of Th2-mediated allergic airway inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Dermatophagoides / immunology
  • Cell Differentiation*
  • Cell Survival
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Granzymes / metabolism
  • Humans
  • Hypersensitivity / immunology*
  • Immune Tolerance
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pyroglyphidae / immunology
  • Receptors, Interleukin-10 / genetics
  • Receptors, Interleukin-10 / metabolism*
  • Signal Transduction
  • Th2 Cells / immunology*

Substances

  • Antigens, Dermatophagoides
  • Receptors, Interleukin-10
  • Interleukin-10
  • Granzymes