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Deciphering the heterogeneity of myeloid cells during neuroinflammation in the single-cell era
Katharina Borst1, Marco Prinz1,2,3
1Institute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
Abstract:
Multiple sclerosis (MS) is a disabling neuroinflammatory disease, which is little understood and lacks a sufficient therapeutic regimen. Myeloid cells have repeatedly shown to play a pivotal role in the disease progression. During homeostasis, only the CNS-resident microglia and CNS-associated macrophages are present in the CNS. Neuroinflammation causes peripheral immune cells to infiltrate the CNS contributing to disease progression and neurological sequelae. The differential involvement of the diverse peripheral and resident myeloid cell subsets to the disease pathogenesis and outcome are highly debated and difficult to assess. However, novel technological advances (new mouse models, single-cell RNA-Sequencing, and CYTOF) have improved the depth of immune profiling, which allows the characterization of distinct myeloid subsets. This review provides an overview of current knowledge on the phenotypes and roles of these different myeloid subsets in neuroinflammatory disease and their therapeutic relevance.
Insights
Multiple sclerosis (MS) involves myeloid cells in the central nervous system (CNS). Understanding these immune cells offers new therapeutic strategies for this disabling neuroinflammatory disease.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Disease Pathogenesis
Background:
- Multiple sclerosis (MS) is a debilitating neuroinflammatory condition with limited treatment options.
- Myeloid cells are crucial in MS pathogenesis, with both resident and infiltrating populations influencing disease progression.
- The precise roles of distinct myeloid cell subsets in MS remain incompletely understood.
Purpose of the Study:
- To review the current understanding of myeloid cell subsets in neuroinflammatory diseases, focusing on multiple sclerosis.
- To elucidate the phenotypes and functions of various myeloid cell populations within the central nervous system (CNS).
- To discuss the therapeutic potential of targeting specific myeloid cell subsets in MS.
Main Methods:
- Review of current scientific literature on myeloid cells in neuroinflammation.
- Integration of data from novel technological advancements, including advanced mouse models, single-cell RNA-sequencing, and cytometry by time-of-flight (CYTOF).
- Characterization of distinct myeloid subsets based on their phenotypes and functions.
Main Results:
- Neuroinflammation leads to peripheral immune cell infiltration into the CNS, exacerbating MS.
- Advanced profiling techniques enable detailed characterization of diverse myeloid cell subsets.
- Specific myeloid populations exhibit differential involvement in MS pathogenesis and outcomes.
Conclusions:
- Myeloid cell subsets play a pivotal role in the progression and outcomes of multiple sclerosis.
- Understanding the heterogeneity of myeloid cells in the CNS is key to developing effective MS therapies.
- Targeting specific myeloid cell subsets presents a promising therapeutic avenue for multiple sclerosis.
