Reduction in CD11c+ microglia correlates with clinical progression in chronic experimental autoimmune demyelination

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease with high variability of clinical symptoms. In most cases MS appears as a relapsing-remitting disease course that at a later stage transitions into irreversible progressive decline of neurologic function. The mechanisms underlying...

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Autores principales:	Florian Mayrhofer, Zhanna Dariychuk, Anthony Zhen, Daniel J. Daugherty, Peter Bannerman, Angela M. Hanson, David Pleasure, Athena Soulika, Wenbin Deng, Olga V. Chechneva
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	CD11c+ microglia EAE progression CNS infiltration p38α sexual dimorphism Glia limitans Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/302d5ae29ee14ef795820b683ac8af09
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spelling	oai:doaj.org-article:302d5ae29ee14ef795820b683ac8af092021-12-04T04:33:12ZReduction in CD11c+ microglia correlates with clinical progression in chronic experimental autoimmune demyelination1095-953X10.1016/j.nbd.2021.105556https://doaj.org/article/302d5ae29ee14ef795820b683ac8af092021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0969996121003053https://doaj.org/toc/1095-953XMultiple sclerosis (MS) is a chronic autoimmune demyelinating disease with high variability of clinical symptoms. In most cases MS appears as a relapsing-remitting disease course that at a later stage transitions into irreversible progressive decline of neurologic function. The mechanisms underlying MS progression remain poorly understood. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS. Here we demonstrate that mice that develop mild EAE after immunization with myelin oligodendrocyte glycoprotein 35-55 are prone to undergo clinical progression around 30 days after EAE induction. EAE progression was associated with reduction in CD11c+ microglia and dispersed coalescent parenchymal infiltration. We found sex-dependent differences mediated by p38α signaling, a key regulator of inflammation. Selective reduction of CD11c+ microglia in female mice with CD11c-promoter driven p38α knockout correlated with increased rate of EAE progression. In protected animals, we found CD11c+ microglia forming contacts with astrocyte processes at the glia limitans and immune cells retained within perivascular spaces. Together, our study identified pathological hallmarks of chronic EAE progression and suggests that CD11c+ microglia may regulate immune cell parenchymal infiltration in autoimmune demyelination.Florian MayrhoferZhanna DariychukAnthony ZhenDaniel J. DaughertyPeter BannermanAngela M. HansonDavid PleasureAthena SoulikaWenbin DengOlga V. ChechnevaElsevierarticleCD11c+ microgliaEAE progressionCNS infiltrationp38α sexual dimorphismGlia limitansNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENNeurobiology of Disease, Vol 161, Iss , Pp 105556- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CD11c+ microglia EAE progression CNS infiltration p38α sexual dimorphism Glia limitans Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	CD11c+ microglia EAE progression CNS infiltration p38α sexual dimorphism Glia limitans Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Florian Mayrhofer Zhanna Dariychuk Anthony Zhen Daniel J. Daugherty Peter Bannerman Angela M. Hanson David Pleasure Athena Soulika Wenbin Deng Olga V. Chechneva Reduction in CD11c+ microglia correlates with clinical progression in chronic experimental autoimmune demyelination
description	Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease with high variability of clinical symptoms. In most cases MS appears as a relapsing-remitting disease course that at a later stage transitions into irreversible progressive decline of neurologic function. The mechanisms underlying MS progression remain poorly understood. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS. Here we demonstrate that mice that develop mild EAE after immunization with myelin oligodendrocyte glycoprotein 35-55 are prone to undergo clinical progression around 30 days after EAE induction. EAE progression was associated with reduction in CD11c+ microglia and dispersed coalescent parenchymal infiltration. We found sex-dependent differences mediated by p38α signaling, a key regulator of inflammation. Selective reduction of CD11c+ microglia in female mice with CD11c-promoter driven p38α knockout correlated with increased rate of EAE progression. In protected animals, we found CD11c+ microglia forming contacts with astrocyte processes at the glia limitans and immune cells retained within perivascular spaces. Together, our study identified pathological hallmarks of chronic EAE progression and suggests that CD11c+ microglia may regulate immune cell parenchymal infiltration in autoimmune demyelination.
format	article
author	Florian Mayrhofer Zhanna Dariychuk Anthony Zhen Daniel J. Daugherty Peter Bannerman Angela M. Hanson David Pleasure Athena Soulika Wenbin Deng Olga V. Chechneva
author_facet	Florian Mayrhofer Zhanna Dariychuk Anthony Zhen Daniel J. Daugherty Peter Bannerman Angela M. Hanson David Pleasure Athena Soulika Wenbin Deng Olga V. Chechneva
author_sort	Florian Mayrhofer
title	Reduction in CD11c+ microglia correlates with clinical progression in chronic experimental autoimmune demyelination
title_short	Reduction in CD11c+ microglia correlates with clinical progression in chronic experimental autoimmune demyelination
title_full	Reduction in CD11c+ microglia correlates with clinical progression in chronic experimental autoimmune demyelination
title_fullStr	Reduction in CD11c+ microglia correlates with clinical progression in chronic experimental autoimmune demyelination
title_full_unstemmed	Reduction in CD11c+ microglia correlates with clinical progression in chronic experimental autoimmune demyelination
title_sort	reduction in cd11c+ microglia correlates with clinical progression in chronic experimental autoimmune demyelination
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/302d5ae29ee14ef795820b683ac8af09
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Reduction in CD11c+ microglia correlates with clinical progression in chronic experimental autoimmune demyelination

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