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bioRxiv · 10.1101/396036

p38α in CD11c+ cells drives sex-specific differences during progression of autoimmune demyelination

Chechneva, O.·Mayrhofer, F.·Dariychuk, Z.·Zhen, A.·Pleasure, D. E.·Deng, W.
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Abstract

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 p38 signaling, a key regulator of inflammation. Selective reduction of CD11c+ microglia in female mice with CD11c-promoter driven p38 knockout (KO) 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 provides evidence on the protective role of CD11c+ microglia in controlling CNS immune cell parenchymal infiltration in autoimmune demyelination.

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Chechneva, O., Mayrhofer, F., Dariychuk, Z., Zhen, A., Pleasure, D. E., Deng, W.. 2018-08-20. p38α in CD11c+ cells drives sex-specific differences during progression of autoimmune demyelination. https://doi.org/10.1101/396036

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