Seasonal Variations in Macrophages/Microglia Underlie Changes in the Mouse Model of Multiple Sclerosis Severity
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ORIGINAL ARTICLE
Seasonal Variations in Macrophages/Microglia Underlie Changes in the Mouse Model of Multiple Sclerosis Severity Nuria Álvarez-Sánchez 1 & Ivan Cruz-Chamorro 1,2 & Ana I. Álvarez-López 1,2 & Antonio López-González 3 & Juan Ramón Lacalle Remigio 4 & Patricia J. Lardone 1,2 & Juan M. Guerrero 1,2,5 & Alicia Martínez-López 1,2 & Antonio Carrillo-Vico 1,2 Received: 27 March 2020 / Accepted: 8 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Both immune and neurodegenerative mechanisms underlie multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). MS/EAE are triggered by encephalitogenic immune cells, including Th1 and Th17 cells, whereas T regulatory (Treg) cells are involved in inflammation resolution. Pro-inflammatory macrophages/microglia also play a deleterious role in the disease. Seasonal variations in MS relapses, active lesions, and pro- and anti-inflammatory cytokine levels have been described in MS patients and have been related with both perinatal and adult exposure to sunlight and other environmental factors. However, some data in EAE mice suggest that these variations might be, at least partially, endogenously determined. Thus, our objective was to study the effect of the season of birth and disease induction on the course of EAE, and immune cell infiltration in the central nervous system (CNS) in myelin oligodendrocyte glycoprotein (MOG35–55)-induced EAE in 8 weeks old, female C57BL/6N mice maintained under constant, controlled conditions. EAE severity as well as pathogenic (Th1, Th17, macrophages/microglia) and protective (Treg) subsets was found to vary according to the season of birth or of EAE induction. Summer-born or summer-immunized animals developed a milder disease, which coincided with variations in numbers of T effector/regulatory subsets, and significantly low numbers of macrophages/microglia. These results suggest that endogenous rhythms in immune responses might cause seasonal variations in EAE severity, and, maybe, in the course of MS, and that they might be related to macrophages/microglia. Keywords EAE/MS . Microglia/macrophages . Seasonal variations . Th1/Th17 . T regulatory cells
Abbreviations BBB Blood-brain barrier CNS Central nervous system CSF Cerebrospinal fluid EAE Experimental autoimmune encephalomyelitis IFN Interferon IL Interleukin
MS MRI NK Th TNF Treg
Multiple sclerosis Magnetic resonance imaging Natural killer cells T helper cell Tumoral necrosis factor T regulatory cells
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02017-x) contains supplementary material, which is available to authorized users. * Antonio Carrillo-Vico [email protected] 1
Instituto de Biomedicina de Sevilla, IBiS, (Universidad de Sevilla, HUVR, Junta de Andalucía, CSIC), Seville, Spain
2
Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Universidad de Sevilla, Seville, Spain
3
Departamento de Neurocirugía, Hospitales Universitari
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