Oestrogen treatment of experimental autoimmune encephalomyelitis requires 17β‐oestradiol‐receptor‐positive B cells that up‐regulate PD‐1 on CD4+ Foxp3+ regulatory T cells |
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Authors: | Sheetal Bodhankar Arthur A. Vandenbark Halina Offner |
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Affiliation: | 1. Neuroimmunology Research, Portland VA Medical Center, , Portland, OR USA;2. Department of Neurology, Oregon Health & Science University, , Portland, OR USA;3. Research Service, Department of Veterans Affairs Medical Center, , Portland, OR USA;4. Department of Molecular Microbiology & Immunology, Oregon Health & Science University, , Portland, OR USA;5. Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, , Portland, OR, USA |
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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; E2) 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. |
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Keywords: | experimental autoimmune encephalomyelitis multiple sclerosis oestrogen and receptors programmed death‐1/programmed death ligand regulatory B cells |
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