Microglial control of astrocytes in response to microbial metabolites

Nature
Veit RothhammerFrancisco J Quintana

Abstract

Microglia and astrocytes modulate inflammation and neurodegeneration in the central nervous system (CNS)1-3. Microglia modulate pro-inflammatory and neurotoxic activities in astrocytes, but the mechanisms involved are not completely understood4,5. Here we report that TGFα and VEGF-B produced by microglia regulate the pathogenic activities of astrocytes in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Microglia-derived TGFα acts via the ErbB1 receptor in astrocytes to limit their pathogenic activities and EAE development. Conversely, microglial VEGF-B triggers FLT-1 signalling in astrocytes and worsens EAE. VEGF-B and TGFα also participate in the microglial control of human astrocytes. Furthermore, expression of TGFα and VEGF-B in CD14+ cells correlates with the multiple sclerosis lesion stage. Finally, metabolites of dietary tryptophan produced by the commensal flora control microglial activation and TGFα and VEGF-B production, modulating the transcriptional program of astrocytes and CNS inflammation through a mechanism mediated by the aryl hydrocarbon receptor. In summary, we identified positive and negative regulators that mediate the microglial control of astrocytes. Moreover, these f...Continue Reading

References

Jun 28, 2000·Progress in Neurobiology·M P Junier
Sep 17, 2002·Journal of Neuropathology and Experimental Neurology·Sukriti NagJames H Eubanks
Mar 23, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Felix MorIrun R Cohen
Sep 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carolyn S JackJack P Antel
Feb 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·William R WikoffGary Siuzdak
Aug 5, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alexander MildnerMarco Prinz
Dec 20, 2011·Trends in Molecular Medicine·Xuri LiZhongshu Tang
Mar 22, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yaping YanGuang-Xian Zhang
Oct 23, 2012·Nature Neuroscience·Kira I MosherTony Wyss-Coray
Aug 3, 2013·Pharmacological Reviews·Francisco J Quintana, David H Sherr
Mar 25, 2014·Annual Review of Immunology·Brigitta StockingerJoão H Duarte
Apr 10, 2014·Nature Reviews. Neuroscience·Marco Prinz, Josef Priller
Jul 23, 2014·Acta Neuropathologica Communications·Francesco GirolamoMaria Trojano
Sep 14, 2014·Nature Medicine·Lior MayoFrancisco J Quintana
Apr 22, 2015·Nature Reviews. Neuroscience·Michael V Sofroniew
Jun 26, 2015·Nature Neuroscience·Baljit S Khakh, Michael V Sofroniew
Mar 31, 2016·Nature·Mark A AndersonMichael V Sofroniew
Jun 23, 2016·Science Signaling·Ada YesteFrancisco J Quintana
Jun 25, 2016·Science·Orit Matcovitch-NatanIdo Amit
Nov 1, 2016·Nature Immunology·Anne ButtgereitMelanie Greter
Nov 5, 2016·The Journal of Experimental Medicine·Kristina A KigerlPhillip G Popovich
Dec 3, 2016·Nature Reviews. Neuroscience·Lucile Ben Haim, David H Rowitch
Jan 19, 2017·Nature·Shane A LiddelowBen A Barres
Feb 9, 2017·Proceedings of the National Academy of Sciences of the United States of America·Veit RothhammerFrancisco J Quintana
Jun 22, 2017·Immunity·Shane A Liddelow, Ben A Barres
Jan 19, 2018·Immunity·Cristina Gutiérrez-Vázquez, Francisco J Quintana
Jan 24, 2018·Cold Spring Harbor Perspectives in Medicine·Michael A Wheeler, Francisco J Quintana

❮ Previous
Next ❯

Citations

Jun 23, 2018·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Mithilesh Kumar JhaKyoungho Suk
Jun 29, 2018·Nature Reviews. Drug Discovery·Sarah Crunkhorn
Aug 24, 2018·Multiple Sclerosis : Clinical and Laboratory Research·Francisco J Quintana
Jul 18, 2018·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Rajan PatelRobert Krencik
Oct 3, 2018·Expert Opinion on Drug Metabolism & Toxicology·Ramy K AzizMarwa T ElRakaiby
Dec 7, 2018·The Journal of Experimental Medicine·Geoffrey T Norris, Jonathan Kipnis
Nov 6, 2018·The Journal of Experimental Medicine·Reem Abdel-HaqSarkis K Mazmanian
Jan 10, 2019·International Journal of Molecular Sciences·Stefanie ScheuJudith Alferink
Mar 29, 2019·Journal of Applied Microbiology·M Bostanciklioğlu
Apr 19, 2019·Journal of Leukocyte Biology·Aline L PachecoKarina R Bortoluci
Apr 27, 2019·Annual Review of Immunology·Eric M BrownRamnik J Xavier
Feb 15, 2019·Nature Reviews. Drug Discovery·Michael PlattenChristiane A Opitz
Jul 7, 2019·Acta Neuropathologica Communications·Thomas VogelsTomáš Hromádka
Jul 19, 2019·Multiple Sclerosis : Clinical and Laboratory Research·Carlos R Camara-LemarroyV Wee Yong
Jun 7, 2019·The Journal of Biological Chemistry·Un-Ho JinStephen Safe
Jan 9, 2019·EMBO Molecular Medicine·Nicole ReichenbachGabor C Petzold
Jul 25, 2018·The EMBO Journal·Nikolaos Dokalis, Marco Prinz
Oct 30, 2019·Metabolomics : Official Journal of the Metabolomic Society·Manuela SimonatoPaola Cogo
Jan 21, 2020·Glia·Hélène HirbecCarole Escartin
Jan 23, 2020·Multiple Sclerosis : Clinical and Laboratory Research·Pavan Bhargava, Daniel C Anthony
Oct 17, 2019·Inflammopharmacology·Xiao-Song WangHai-Feng Pan
Feb 14, 2020·Nature·Michael A WheelerFrancisco J Quintana
Mar 18, 2020·Glia·Daniel Erny, Marco Prinz
Mar 19, 2020·International Journal of Molecular Sciences·Nicte Alaide Ramos-GarcíaMónica Adriana Torres-Ramos
Apr 24, 2020·Current Opinion in Neurology·Martina AbsintaBruce D Trapp
May 15, 2020·Stroke; a Journal of Cerebral Circulation·Corinne BenakisJosef Anrather
Jun 24, 2020·Journal of Leukocyte Biology·Idy H T HoXiaodong Liu
May 14, 2020·Journal of Neurochemistry·Manal AlaameryFrancisco J Quintana
Dec 14, 2018·The Journal of Experimental Medicine·Kevin A Guttenplan, Shane A Liddelow
Nov 23, 2018·International Journal of Molecular Sciences·Egle CekanaviciuteSylvain V Costes
Jan 9, 2019·Nature Medicine·Xu Chen, Li Gan
Jan 9, 2019·Frontiers in Neuroscience·Md Habibur RahmanKyoungho Suk
Feb 6, 2019·Nature Reviews. Immunology·Veit Rothhammer, Francisco J Quintana
Apr 11, 2019·Frontiers in Pharmacology·Jiaying WangQiaojun He
May 9, 2019·Journal of Dental Anesthesia and Pain Medicine·Koichi Iwata, Masamichi Shinoda

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
RNA-seq
flow cytometry
PMA
immunoprecipitation

Software Mentioned

Image J
Cuffnorm
R
ggplot
Gene
Prism
Imaris
Volocity
GraphPad
Cuffquant

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.