Document Detail


Oestrogen treatment of experimental autoimmune encephalomyelitis requires 17β-oestradiol-receptor-positive B cells that up-regulate PD-1 on CD4+ Foxp3+ regulatory T cells.
MedLine Citation:
PMID:  23039230     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Sheetal Bodhankar; Arthur A Vandenbark; Halina Offner
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Immunology     Volume:  137     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-21     Completed Date:  2013-02-26     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  282-93     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
B-Lymphocytes / drug effects,  immunology,  metabolism*
Encephalomyelitis, Autoimmune, Experimental / drug therapy*,  immunology
Estradiol / pharmacology,  therapeutic use*
Female
Forkhead Transcription Factors / analysis,  metabolism
Mice
Mice, Inbred C57BL
Programmed Cell Death 1 Receptor / metabolism*
Receptors, Estradiol / analysis,  metabolism*
T-Lymphocytes, Regulatory / drug effects,  immunology,  metabolism*
Up-Regulation* / drug effects
Grant Support
ID/Acronym/Agency:
NS045445/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/Pdcd1 protein, mouse; 0/Programmed Cell Death 1 Receptor; 0/Receptors, Estradiol; 4TI98Z838E/Estradiol
Comments/Corrections

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