title: Oestrogen treatment of experimental autoimmune encephalomyelitis requires 17β-oestradiol-receptor-positive B cells that up-regulate PD-1 on CD4+ Foxp3+ regulatory T cells.
abstract: It is now well accepted that sex hormones have immunoregulatory activity and may prevent exacerbations in multiple sclerosis during pregnancy. Our previous studies demonstrated that oestrogen (17β-oestradiol; E(2) ) protection against experimental autoimmune encephalomyelitis (EAE) is mediated mainly through oestrogen receptor-α (ERα) and the membrane receptor G-protein-coupled receptor 30 (GPR30) and is abrogated in the absence of B cells and the co-inhibitory receptor, Programmed Death-1 (PD-1). To critically evaluate the cell source of the E2 and PD-1 co-inhibitory pathways in EAE regulation, we assessed the requirement for ERs on transferred B cells and downstream effects on expression of PD-1/PD-ligand on CD4+ Foxp3+ regulatory T (Treg) cells in B-cell-replenished, E2-treated B-cell-deficient (μMT-/-) mice with EAE. The results clearly demonstrated involvement of ERα and GPR30 on transferred B cells that mediated the protective E2 treatment effect on EAE and further showed an E2-mediated B-cell-dependent up-regulation of PD-1 on CD4+ Foxp3+ Treg cells. These findings identify regulatory B-cell populations as key players in potentiating Treg-cell activity during E2-mediated protection against EAE.
authors.affiliation: Neuroimmunology Research, Portland VA Medical Center, Portland, OR 97239, USA.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Bodhankar
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D011959:Receptors, Estradiol / Q000032:analysis / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011959:Receptors, Estradiol; D004958:Estradiol