Related Experiment Video
Updated: Dec 8, 2025
Author Spotlight: Creating a Versatile Experimental Autoimmune Encephalomyelitis Model Relevant for Both Male and Female Mice
Published on: October 13, 2023
Sex-Specific Effects of Microglia-Like Cell Engraftment during Experimental Autoimmune Encephalomyelitis
Jinming Han1, Keying Zhu1, Kai Zhou2
1Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, S-171 76 Stockholm, Sweden.
Abstract:
Multiple sclerosis (MS) is a chronic neuroinflammatory disorder of the central nervous system (CNS) that usually presents in young adults and predominantly in females. Microglia, a major resident immune cell in the CNS, are critical players in both CNS homeostasis and disease. We have previously demonstrated that microglia can be efficiently depleted by the administration of tamoxifen in Cx3cr1CreER/+Rosa26DTA/+ mice, with ensuing repopulation deriving from both the proliferation of residual CNS resident microglia and the engraftment of peripheral monocyte-derived microglia-like cells. In this study, tamoxifen was administered to Cx3cr1CreER/+Rosa26DTA/+ and Cx3cr1CreER/+ female and male mice. Experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, was induced by active immunization with myelin oligodendrocyte glycoprotein (MOG) one month after tamoxifen injections in Cx3cr1CreER/+Rosa26DTA/+ mice and Cx3cr1CreER/+ mice, a time point when the CNS niche was colonized by microglia derived from both CNS microglia and peripherally-derived macrophages. We demonstrate that engraftment of microglia-like cells following microglial depletion exacerbated EAE in Cx3cr1CreER/+Rosa26DTA/+ female mice as assessed by clinical symptoms and the expression of CNS inflammatory factors, but these findings were not evident in male mice. Higher major histocompatibility complex class II expression and cytokine production in the female CNS contributed to the sex-dependent EAE severity in mice following engraftment of microglia-like cells. An underestimated yet marked sex-dependent microglial activation pattern may exist in the injured CNS during EAE.
Insights
Microglial depletion and repopulation worsened experimental autoimmune encephalomyelitis (EAE) in female mice, not males, due to sex-specific inflammatory responses in the central nervous system (CNS). This highlights sex-dependent microglial activation in neuroinflammation.
Area of Science:
- Neuroimmunology
- Central Nervous System (CNS) Disorders
- Microglia Biology
Background:
- Multiple sclerosis (MS) is a chronic CNS neuroinflammatory disease affecting young adults, predominantly females.
- Microglia, the resident immune cells of the CNS, are key in maintaining homeostasis and disease processes.
- Previous work established efficient microglial depletion and repopulation from residual cells and peripheral monocytes in Cx3cr1CreER/+Rosa26DTA/+ mice.
Purpose of the Study:
- To investigate the impact of microglial repopulation on experimental autoimmune encephalomyelitis (EAE) severity in a sex-dependent manner.
- To analyze the role of CNS inflammatory factors and cellular changes in sex-specific EAE outcomes following microglial depletion and repopulation.
Main Methods:
- Tamoxifen administration to deplete microglia in Cx3cr1CreER/+Rosa26DTA/+ and Cx3cr1CreER/+ mice (female and male).
- Induction of EAE via myelin oligodendrocyte glycoprotein (MOG) immunization one month post-tamoxifen.
- Assessment of clinical EAE symptoms, CNS inflammatory factor expression, and major histocompatibility complex class II (MHC-II) and cytokine production.
Main Results:
- Engraftment of microglia-like cells post-depletion exacerbated EAE in female mice, evidenced by increased clinical symptoms and CNS inflammation.
- These exacerbating effects were not observed in male mice.
- Female mice exhibited higher MHC-II expression and cytokine production in the CNS, contributing to sex-dependent EAE severity.
Conclusions:
- Microglial depletion and subsequent repopulation with microglia-like cells worsen EAE in female mice, suggesting a sex-specific vulnerability.
- Sex-dependent differences in CNS inflammatory responses, particularly MHC-II and cytokine profiles, underlie the observed EAE severity.
- A significant sex-dependent microglial activation pattern may be involved in CNS injury during EAE.
More Related Videos
08:47Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
10:50Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
Published on: March 26, 2019