Treatment with IL-10 producing B cells in combination with E2 ameliorates EAE severity and decreases CNS inflammation in B cell-deficient mice

Metabolic Brain Disease
Jun ZhangHalina Offner

Abstract

Clinical improvement during pregnancy in multiple sclerosis (MS) patients suggests that sex hormones exert potent regulatory effects on autoimmune function. Our previous studies demonstrated that estrogen- (17β-estradiol; E2) mediated protection against experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, hinges on the B cells, leading to elevated numbers of IL-10 secreting CD1d(hi)CD5(+) B regulatory cells (Bregs) in wild type mice. Our data show that co-administration of E2 and IL-10(+) B cells ameliorates EAE disease severity and limits CNS infiltrating leukocytes in B cell deficient mice. Additionally, treatment with E2 and Bregs reduces demyelination and dramatically decreases the proportion of CD11b(+)CD45(hi) activated microglia/macrophages found in the CNS of immunized animals compared to vehicle, E2 or Breg cells alone. Furthermore, mice given E2 and Bregs exhibit increased numbers of peripheral programmed death-1 positive CD4(+)Foxp3(+) regulatory T cells (Tregs) and up-regulation of programmed death receptor-ligand-1 and CD80 expression on monocytes. Our study suggests IL-10 producing Bregs have powerful therapeutic potential as an agent against EAE when augmented with E2 treatment.

References

Jan 1, 1994·Annals of Neurology·O Abramsky
Dec 1, 1996·The Journal of Experimental Medicine·S D WolfC A Janeway
Jul 31, 1998·The New England Journal of Medicine·C ConfavreuxT Moreau
Aug 30, 2001·Nature Immunology·L Steinman
Feb 2, 2002·Stroke; a Journal of Cerebral Circulation·Marilena CampanellaMassimiliano Beltramo
Sep 24, 2002·Nature Immunology·Simon FillatreauStephen M Anderton
Nov 3, 2004·The Journal of Experimental Medicine·Muhaimin Rifa'iHaruhiko Suzuki
Sep 7, 2006·The Journal of Clinical Investigation·Estelle BettelliVijay K Kuchroo
Dec 13, 2006·The European Journal of Neuroscience·K B MarquesA L R Oliveira
Jan 31, 2007·Annals of the New York Academy of Sciences·Halina Offner, Magdalena Polanczyk
May 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Martin DuddyAmit Bar-Or
Jun 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jamie G EvansClaudia Mauri
Aug 7, 2007·Nature Medicine·Martin S WeberScott S Zamvil
Sep 20, 2008·The Journal of Clinical Investigation·Takashi MatsushitaThomas F Tedder
Oct 31, 2008·Lancet·Alastair Compston, Alasdair Coles
Jul 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rajat MadanChristopher L Karp
Mar 9, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Min YangLiwei Lu
Jan 10, 2012·Annual Review of Immunology·Claudia Mauri, Anneleen Bosma
Jan 18, 2012·Nature Reviews. Neurology·Katy Malpass
Mar 10, 2012·Neurology·Martin DaumerRhonda Voskuhl
Apr 10, 2013·Arthritis Research & Therapy·Ioannis KalampokisThomas F Tedder
May 4, 2013·Metabolic Brain Disease·Sheetal BodhankarHalina Offner
Sep 7, 2013·Journal of Clinical & Cellular Immunology·Sheetal BodhankarHalina Offner
Jan 30, 2014·Annual Review of Immunology·Debasis NayakDorian B McGavern
Jul 13, 2014·Methods in Molecular Biology·Avijit Ray, Sreemanti Basu

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Citations

Jul 25, 2017·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Andrew D GaudetPhillip G Popovich
Jan 10, 2018·Immunology·Hilary A SeifertHalina Offner
May 20, 2016·Endocrine Reviews·Alessandro VillaAdriana Maggi
Apr 27, 2016·Journal of Neuroscience Research·Jinming HanTao Jin
Mar 7, 2017·Frontiers in Immunology·Ruth Marian Guzman-Genuino, Kerrilyn R Diener
Jul 22, 2018·International Journal of Molecular Sciences·Ana Esteve-SoléLaia Alsina
May 14, 2020·International Journal of Molecular Sciences·Yingzhi Gu, Xiaozhe Han
Oct 31, 2019·Journal of Neuroinflammation·Hilary A SeifertHalina Offner
Jun 20, 2018·Metabolic Brain Disease·Hilary A SeifertHalina Offner
Dec 2, 2020·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Chunping CuiWei Qiu

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