MHC class I and MHC class II reporter mice enable analysis of immune oligodendroglia in mouse models of multiple sclerosis
Abstract
Oligodendrocytes and their progenitors upregulate MHC pathways in response to inflammation, but the frequency of this phenotypic change is unknown and the features of these immune oligodendroglia are poorly defined. We generated MHC class I and II transgenic reporter mice to define their dynamics in response to inflammatory demyelination, providing a means to monitor MHC activation in diverse cell types in living mice and define their roles in aging, injury and disease.
Data availability
Sequencing data has been deposited in GEO under the accession code GSE213739Code used to analyze sequencing data was uploaded at Source Code File 1All data generated or analyzed during this study are included in manuscript source data files
Article and author information
Author details
Funding
National Institutes of Health (NIA AG072305)
- Dwight E Bergles
National Multiple Sclerosis Society (FAN-1707-28857)
- Em P Harrington
Dr. Miriam and Sheldon G Adelson Medical Research Foundation
- Dwight E Bergles
National Science Foundation
- Riley B Catenacci
National Institutes of Health (R01 NS041435)
- Peter A Calabresi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal procedures were performed according to protocols approved by the Johns Hopkins Animal Care and Use Committee protocol #MO22M158.
Copyright
© 2023, Harrington et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,959
- views
-
- 448
- downloads
-
- 17
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Immunology and Inflammation
Macrophages control intracellular pathogens like Salmonella by using two caspase enzymes at different times during infection.
-
- Immunology and Inflammation
- Medicine
Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between PE and GDM is still lacking. In this study, cytometry by time of flight indicated that the frequencies of memory-like Th17 cells (CD45RA−CCR7+IL-17A+CD4+), memory-like CD8+ T cells (CD38+CXCR3−CCR7+Helios−CD127−CD8+) and pro-inflam Macs (CD206−CD163−CD38midCD107alowCD86midHLA-DRmidCD14+) were increased, while the frequencies of anti-inflam Macs (CD206+CD163−CD86midCD33+HLA-DR+CD14+) and granulocyte myeloid-derived suppressor cells (gMDSCs, CD11b+CD15hiHLA-DRlow) were decreased in the placenta of PE compared with that of normal pregnancy (NP), but not in that of GDM or GDM&PE. The pro-inflam Macs were positively correlated with memory-like Th17 cells and memory-like CD8+ T cells but negatively correlated with gMDSCs. Single-cell RNA sequencing revealed that transferring the F4/80+CD206− pro-inflam Macs with a Folr2+Ccl7+Ccl8+C1qa+C1qb+C1qc+ phenotype from the uterus of PE mice to normal pregnant mice induced the production of memory-like IL-17a+Rora+Il1r1+TNF+Cxcr6+S100a4+CD44+ Th17 cells via IGF1–IGF1R, which contributed to the development and recurrence of PE. Pro-inflam Macs also induced the production of memory-like CD8+ T cells but inhibited the production of Ly6g+S100a8+S100a9+Retnlg+Wfdc21+ gMDSCs at the maternal–fetal interface, leading to PE-like symptoms in mice. In conclusion, this study revealed the PE-specific immune cell network, which was regulated by pro-inflam Macs, providing new ideas about the pathogenesis of PE.