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Author Spotlight: Creating a Versatile Experimental Autoimmune Encephalomyelitis Model Relevant for Both Male and Female Mice
Published on: October 13, 2023
Cognate microglia-T cell interactions shape the functional regulatory T cell pool in experimental autoimmune
Zhana Haimon1, Gal Ronit Frumer1, Jung-Seok Kim1
1Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel.
Abstract:
Microglia, the parenchymal brain macrophages of the central nervous system, have emerged as critical players in brain development and homeostasis. The immune functions of these cells, however, remain less well defined. We investigated contributions of microglia in a relapsing-remitting multiple sclerosis paradigm, experimental autoimmune encephalitis in C57BL/6 x SJL F1 mice. Fate mapping-assisted translatome profiling during the relapsing-remitting disease course revealed the potential of microglia to interact with T cells through antigen presentation, costimulation and coinhibition. Abundant microglia-T cell aggregates, as observed by histology and flow cytometry, supported the idea of functional interactions of microglia and T cells during remission, with a bias towards regulatory T cells. Finally, microglia-restricted interferon-γ receptor and major histocompatibility complex mutagenesis significantly affected the functionality of the regulatory T cell compartment in the diseased central nervous system and remission. Collectively, our data establish critical non-redundant cognate and cytokine-mediated interactions of microglia with CD4+ T cells during autoimmune neuroinflammation.
Insights
Microglia, the brain's immune cells, interact with T cells during autoimmune neuroinflammation, influencing disease progression and remission in a multiple sclerosis model. These interactions are critical for regulating T cell responses in the central nervous system.
Area of Science:
- Neuroimmunology
- Central Nervous System (CNS) Immunology
Background:
- Microglia are key immune cells in the brain, essential for development and homeostasis.
- Their specific roles in immune functions, particularly in neuroinflammatory diseases, require further elucidation.
Purpose of the Study:
- To investigate the functional contributions of microglia in a relapsing-remitting multiple sclerosis model.
- To define the interactions between microglia and T cells during autoimmune neuroinflammation.
Main Methods:
- Utilized experimental autoimmune encephalitis in mice as a relapsing-remitting multiple sclerosis paradigm.
- Employed fate mapping-assisted translatome profiling to analyze cellular interactions.
- Histology and flow cytometry were used to identify microglia-T cell aggregates.
Main Results:
- Microglia were found to interact with T cells via antigen presentation, costimulation, and coinhibition.
- Abundant microglia-T cell aggregates were observed, particularly with regulatory T cells during remission.
- Mutagenesis of interferon-γ receptor and MHC in microglia impacted regulatory T cell function.
Conclusions:
- Microglia engage in critical, non-redundant interactions with CD4+ T cells during autoimmune neuroinflammation.
- These interactions involve both direct cell-cell contact and cytokine-mediated signaling.
- Microglia play a significant role in modulating T cell responses within the CNS during disease and remission.
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