Seasonal Variations in Macrophages/Microglia Underlie Changes in the Mouse Model of Multiple Sclerosis Severity
Nuria Álvarez-Sánchez1, Ivan Cruz-Chamorro1,2, Ana I Álvarez-López1,2
1Instituto de Biomedicina de Sevilla, IBiS, (Universidad de Sevilla, HUVR, Junta de Andalucía, CSIC), Seville, Spain.
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.
Insights
Seasonal factors influence experimental autoimmune encephalomyelitis (EAE) severity. Animals born or immunized in summer experienced milder EAE, linked to immune cell variations, particularly lower macrophage/microglia infiltration.
Area of Science:
- Neuroimmunology
- Immunology
- Neuroscience
Background:
- Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), involve complex immune and neurodegenerative processes.
- Immune cells like Th1, Th17, T regulatory (Treg) cells, and macrophages/microglia play critical roles in MS/EAE pathogenesis and resolution.
- While seasonal variations in MS are observed, their origins (environmental vs. endogenous) remain debated.
Purpose of the Study:
- To investigate the impact of birth season and disease induction season on EAE course and central nervous system (CNS) immune cell infiltration.
- To determine if endogenous rhythms, rather than solely environmental factors, contribute to seasonal variations in EAE.
Main Methods:
- Induction of myelin oligodendrocyte glycoprotein (MOG35-55)-induced EAE in 8-week-old female C57BL/6N mice.
- Controlled housing conditions to isolate the effects of season of birth and immunization.
- Analysis of EAE clinical scores and quantification of immune cell subsets (Th1, Th17, Treg, macrophages/microglia) in the CNS.
Main Results:
- EAE severity and immune cell infiltration varied significantly based on the season of birth or EAE induction.
- Milder EAE was observed in summer-born or summer-immunized mice.
- These milder cases correlated with altered T effector/regulatory cell populations and notably reduced numbers of macrophages/microglia in the CNS.
Conclusions:
- Endogenous biological rhythms may contribute to seasonal variations in EAE severity.
- Macrophages/microglia infiltration in the CNS appears to be a key factor influenced by seasonal effects in EAE.
- Findings suggest potential endogenous seasonal influences on MS disease activity.
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