Estrogen induces multiple regulatory B cell subtypes and promotes M2 microglia and neuroprotection during experimental autoimmune encephalomyelitis

J Neuroimmunol. 2016 Apr 15:293:45-53. doi: 10.1016/j.jneuroim.2016.02.009. Epub 2016 Feb 13.

Abstract

Sex hormones promote immunoregulatory effects on multiple sclerosis. The current study evaluated estrogen effects on regulatory B cells and resident CNS microglia during experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrate an estrogen-dependent induction of multiple regulatory B cell markers indicative of IL-10 dependent as well as IFN-γ dependent pathways. Moreover, although estrogen pretreatment of EAE mice inhibited the infiltration of pro-inflammatory cells into the CNS, it enhanced the frequency of regulatory B cells and M2 microglia. Our study suggests that estrogen has a broad effect on the development of regulatory B cells during EAE, which in turn could promote neuroprotection.

Keywords: EAE; Estrogen; IFN-γ; IL-10; Microglia; Regulatory B cell.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes, Regulatory / drug effects*
  • B-Lymphocytes, Regulatory / metabolism
  • Brain / pathology
  • Cell Proliferation / drug effects
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Estradiol / therapeutic use*
  • Freund's Adjuvant / toxicity
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects*
  • Microglia / metabolism
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Myelin-Oligodendrocyte Glycoprotein / toxicity
  • Peptide Fragments / immunology
  • Peptide Fragments / toxicity
  • Pertussis Toxin / toxicity
  • RNA, Messenger / metabolism
  • Spinal Cord / cytology
  • Spleen / cytology
  • Statistics, Nonparametric
  • Time Factors

Substances

  • Cytokines
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • RNA, Messenger
  • myelin oligodendrocyte glycoprotein (35-55)
  • Estradiol
  • Freund's Adjuvant
  • Pertussis Toxin