Silencing IFN-γ binding/signaling in astrocytes versus microglia leads to opposite effects on central nervous system autoimmunity

The Journal of Immunology : Official Journal of the American Association of Immunologists
Xiaoli DingAbdolmohamad Rostami

Abstract

IFN-γ, the hallmark cytokine of Th1 cells, plays an important role in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Thus far, the role of IFN-γ in EAE has been largely studied through its effects on immune cells, whereas much less is known about its effects on CNS cells, especially in vivo. In this study, we dissected the in vivo effects and mechanisms of IFN-γ binding/signaling in astrocytes and microglia, and found that IFN-γ signaling in these cell types has opposite effects in EAE pathogenesis. Silencing IFN-γ binding/signaling in astrocytes alleviated EAE, whereas in microglia, and likely in some infiltrating macrophages, it increased disease severity. Silencing IFN-γ signaling in astrocytes resulted in diminished expression of chemokines and fewer inflammatory cells infiltrating into the CNS, whereas blocking IFN-γ binding/signaling in microglia, probably infiltrating macrophages as well, increased disease severity through augmented activation and proliferation of microglia. Further, blocking IFN-γ binding/signaling in astrocytes alleviated both Th1- and Th17-mediated adoptive EAE, indicating an important role for IFN-γ signaling in astrocytes in autoimmune CNS inflammation. Thus,...Continue Reading

References

Nov 1, 1994·The Journal of Experimental Medicine·M K RackeM Röcken
Feb 1, 1997·Molecular Neurobiology·B PopkoA M Garcia
Nov 29, 2001·Multiple Sclerosis : Clinical and Laboratory Research·S SkurkovichE Gusev
Oct 9, 2002·The Journal of Experimental Medicine·Yosef RefaeliAbul K Abbas
Feb 13, 2003·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Gareth R JohnCelia F Brosnan
Oct 4, 2003·Journal of Leukocyte Biology·Kate SchroderDavid A Hume
Jun 17, 2005·Journal of Neuroscience Research·Eugene D PonomarevBonnie N Dittel
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yutaka KomiyamaYoichiro Iwakura
Jul 6, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christophe M DerooseVeerle Baekelandt
Aug 15, 2006·The Journal of Clinical Investigation·Zhaojun WangJingwu Z Zhang
Oct 6, 2007·Nature Reviews. Immunology·Alan G Baxter
Apr 1, 2008·Neurobiology of Aging·Sadayuki HashiokaPatrick L McGeer
Jun 3, 2008·Cellular and Molecular Life Sciences : CMLS·A NairS D Miller
Sep 9, 2008·Trends in Immunology·Hilde KelchtermansPatrick Matthys
Oct 15, 2008·The Journal of Experimental Medicine·Jason R LeesJohn H Russell
Apr 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Makoto TsudaKazuhide Inoue
Nov 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Andres Gottfried-BlackmoreKaren Bulloch
Jun 12, 2010·European Journal of Immunology·Mark A KroenkeBenjamin M Segal
Jul 6, 2010·Biochimica Et Biophysica Acta·Amy E Lovett-RackeMichael K Racke
Oct 15, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yaping YanHui Xu
Oct 19, 2010·Brain, Behavior, and Immunity·Mark A Kroenke, Benjamin M Segal
Feb 1, 2011·Nature Immunology·Keiji HirotaBrigitta Stockinger
Mar 22, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yaping YanGuang-Xian Zhang
Oct 23, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Friederike EbnerRobert Nitsch
Oct 30, 2013·Frontiers in Immunology·Andrea J SantJacqueline Tung
Nov 16, 2013·Neuroscience·I LundgaardM Nedergaard
Sep 14, 2014·Nature Medicine·Lior MayoFrancisco J Quintana
Oct 9, 2014·Nature Medicine·Abdolmohamad Rostami, Bogoljub Ciric

❮ Previous
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Citations

Dec 24, 2015·Frontiers in Neurology·Danielle E HarlowAugusto A Miravalle
Dec 6, 2016·Nature Reviews. Immunology·Burkhard BecherJoan Goverman
Sep 30, 2017·International Journal of Molecular Sciences·Tobias Koeniger, Stefanie Kuerten
Oct 16, 2019·The Journal of Experimental Medicine·Catriona A WagnerJoan M Goverman
Apr 1, 2020·Cells·Affan Ali SherKevin M Coombs
Jun 13, 2019·Nature Communications·Dieter Henrik HeilandOliver Schnell
Feb 10, 2018·Frontiers in Immunology·Ying Fu, Yaping Yan
Jan 16, 2019·Nature Communications·Sarah C StarossomSamia J Khoury
Apr 23, 2020·Frontiers in Cellular Neuroscience·Elisabeth TraiffortYousra Laouarem
Jul 17, 2016·Clinical Reviews in Allergy & Immunology·Carlo Selmi
Sep 26, 2020·Frontiers in Cellular Neuroscience·Melanie J PlastiniRoberta Brambilla
May 16, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anna KudriaevaAlexey Belogurov
Oct 12, 2020·Neurochemical Research·Micheli Stéfani ZarzeckiCristiano Ricardo Jesse
Feb 26, 2021·The Journal of Experimental Medicine·Daria KveštakStipan Jonjić
Jul 6, 2016·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Emily R PiersonJoan M Goverman
Feb 2, 2021·Annual Review of Immunology·Valeria RamagliaJennifer L Gommerman

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