IL-10 derived from CD1dhiCD5⁺ B cells regulates experimental autoimmune myasthenia gravis

J Neuroimmunol. 2015 Dec 15:289:130-8. doi: 10.1016/j.jneuroim.2015.10.023. Epub 2015 Oct 31.

Abstract

IL-10-competent subset within CD1d(hi)CD5(+) B cells, also known as B10 cells, has been shown to regulate autoimmune diseases. In our previous study, adoptive transfer of CD1d(hi)CD5(+) B cells expanded in vivo by GM-CSF prevented and suppressed experimental autoimmune myasthenia gravis (EAMG). The goal of this study was to further examine the role and mechanism of IL-10 in the regulatory function of B10 cells in EAMG. We found that only IL-10 competent CD1d(hi)CD5(+) B cells sorted from WT mice, but not IL-10 deficient CD1d(hi)CD5(+) B cells exhibited regulatory function in vitro and in vivo. Adoptive transfer of IL-10 competent CD1d(hi)CD5(+) B cells led to higher frequency of Tregs and B10 cells, and low levels of proinflammatory cytokines and autoantibody production. We conclude that IL-10 production within CD1d(hi)CD5(+) B cells plays an important role in immune regulation of EAMG.

Keywords: Acetylcholine receptor; Autoimmune disease; Cytokines; Immune tolerance; Regulatory B cells; Tregs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods
  • Animals
  • Antigens, CD1d / metabolism*
  • B-Lymphocyte Subsets / chemistry*
  • CD5 Antigens / metabolism*
  • Cell Proliferation / physiology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Skeletal / metabolism
  • Myasthenia Gravis, Autoimmune, Experimental / chemically induced
  • Myasthenia Gravis, Autoimmune, Experimental / immunology*
  • Myasthenia Gravis, Autoimmune, Experimental / pathology*
  • Myasthenia Gravis, Autoimmune, Experimental / physiopathology
  • Peptide Fragments / immunology
  • Receptors, Nicotinic / immunology

Substances

  • Antigens, CD1d
  • CD1D protein, human
  • CD5 Antigens
  • Cytokines
  • Peptide Fragments
  • Receptors, Nicotinic
  • Torpedo acetylcholine receptor, alpha-subunit 1-20
  • Interleukin-10