Epitopes described in "Estrogen-induced protection against experimental autoimmune encephalomyelitis is abrogated in the absence of B cells."

Article Authors:Sheetal Bodhankar; Chunhe Wang; Arthur A Vandenbark; Halina Offner
Article Title:Estrogen-induced protection against experimental autoimmune encephalomyelitis is abrogated in the absence of B cells.
Reference Detail
Reference ID:1021999
Abstract:Increased remissions in multiple sclerosis (MS) during pregnancy suggest that elevated levels of sex steroids exert immunoregulatory activity. Estrogen (E2=17-estradiol) protects against experimental autoimmune encephalomyelitis (EAE), but the cellular basis for E2-induced protection remains unclear. Studies demonstrate that depletion of B cells prior to induction of EAE exacerbates disease severity, implicating regulatory B cells. We thus evaluated pathogenic and E2-induced protective mechanisms in B-cell-deficient (MT(-/-)) mice. EAE-protective effects of E2 were abrogated in MT(-/-) mice, with no reduction in disease severity, cellular infiltration or pro-inflammatory factors in the central nervous system compared to untreated controls. E2 treatment of WT mice selectively upregulated expression of PD-L1 on B cells and increased the percentage of IL-10-producing CD1d(high) CD5(+) regulatory B cells. Upregulation of PD-L1 was critical for E2-mediated protection since E2 did not inhibit EAE in PD-L1(-/-) mice. Direct treatment of B cells with E2 significantly reduced proliferation of MOG(35-55)-specific T cells that required estrogen receptor- (ER). These results demonstrate, for the first time, a requirement for B cells in E2-mediated protection against EAE involving direct E2 effects on regulatory B cells mediated through ER and the PD-1/PD-L1 negative co-stimulatory pathway. E2-primed B cells may represent an important regulatory mechanism in MS and have strong implications for women receiving current MS therapies that cause B-cell depletion.
Reference Type:Literature
PubMed ID:21413005
Journal:Eur J Immunol
Journal Volume:41
Article Pages:1165-75
Journal ISSN:0014-2980
Article Chemical List:Antigens, CD1d;Antigens, CD274;Antigens, CD5;Antigens, CD80;Cd1d1 protein, mouse;Cd274 protein, mouse;Estrogens;Membrane Glycoproteins;Peptides;Estradiol
Article MeSH List:Animals; Antigens, CD1d(immunology); Antigens, CD274; Antigens, CD5(immunology); Antigens, CD80(immunology); B-Lymphocytes(immunology); Cells, Cultured; Encephalomyelitis, Autoimmune, Experimental(immunology); Estradiol(immunology); Estrogens(immunology); Female; Membrane Glycoproteins(deficiency; immunology); Mice; Mice, Inbred C57BL; Mice, Knockout; Peptides(deficiency; immunology); Spleen(immunology)
Curation Last Updated:2015-07-30 20:39:28