The regulatory B cell-mediated peripheral tolerance maintained by mast cell IL-5 suppresses oxazolone-induced contact hypersensitivity

Sci Adv. 2019 Jul 17;5(7):eaav8152. doi: 10.1126/sciadv.aav8152. eCollection 2019 Jul.

Abstract

The function of regulatory immune cells in peripheral tissues is crucial to the onset and severity of various diseases. Interleukin-10 (IL-10)-producing regulatory B (IL-10+ Breg) cells are known to suppress various inflammatory diseases. However, evidence for the mechanism by which IL-10+ Breg cells are generated and maintained is still very limited. Here, we found that IL-10+ Breg cells suppress the activation of IL-13-producing type 2 innate lymphoid cells (IL-13+ ILC2s) in an IL-10-dependent manner in mice with oxazolone-induced severe contact hypersensitivity (CHS). Mast cell (MC) IL-5 was important for maintaining the population of IL-10+ Breg cells in peripheral lymphoid tissues. Overall, these results uncover a previously unknown mechanism of MCs as a type of immunoregulatory cell and elucidate the cross-talk among MCs, IL-10+ Breg cells, and IL-13+ ILC2s in CHS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes, Regulatory / immunology*
  • B-Lymphocytes, Regulatory / metabolism*
  • Cytokines / metabolism
  • Dermatitis, Contact / etiology*
  • Dermatitis, Contact / metabolism*
  • Dermatitis, Contact / pathology
  • Disease Models, Animal
  • Fluorescent Antibody Technique
  • Immunoglobulin Isotypes / immunology
  • Interleukin-5 / metabolism*
  • Male
  • Mast Cells / immunology*
  • Mast Cells / metabolism*
  • Mice
  • Mice, Knockout
  • Oxazolone / adverse effects*
  • Peripheral Tolerance*

Substances

  • Cytokines
  • Immunoglobulin Isotypes
  • Interleukin-5
  • Oxazolone