Related Experiment Video
Updated: May 16, 2025
Murine Colitis Modeling using Dextran Sulfate Sodium DSS
Published on: January 19, 2010
ERMAP attenuates DSS-induced colitis in mice by regulating macrophage and T cell functions
Lu Xia1,2,3, Yiwen Pan2, Xianbin Wang2
1Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University, 6 Ankang Avenue, Guian New District, Guizhou, 561113, China.
Background & Aims:
Both macrophages and T cells play a critical role in inflammatory bowel disease (IBD) development. Since our previous studies have shown that a novel immune checkpoint molecule erythrocyte membrane-associated protein (ERMAP) affects macrophage polarization and negatively regulates T cell responses, we investigated the effects of ERMAP on DSS-induced colitis progression in mice.
Methods:
C57BL/6 mice developed a dextran sodium sulfate (DSS) colitis model, treated with control Fc protein (Control Ig) and ERMAP-Fc fusion protein (ERMAP-Ig) for 12 days to assess colitis severity by disease activity index (DAI), weight loss, colon length, histology, flow cytometry, Q-PCR, WB, ELISA, and the effect of adoptive transfer of ERMAP knockout mice (ERMAP-/-) peritoneal macrophages on DSS colitis mice. In vitro, the effects of the RAW264.7 macrophage cell line that interfered with ERMAP expression on macrophage polarization and T cells were analyzed by flow cytometry.
Results:
We show here that administration of ERMAP protein significantly increases the proportion of anti-inflammatory M2-type macrophages and inhibits T cell activation and proliferation in DSS-induced colitis mice. Knockdown of ERMAP in RAW264.7 macrophages reduces M2-type macrophage polarization and increases T cell responses. Adoptive transfer of macrophages from ERMAP-/- exacerbates DSS-induced colitis. Global gene expression analysis by RNA-seq shows that ERMAP inhibits the NOD-like receptor (NLR) protein family pathway in macrophages.
Conclusions:
In summary, our results suggest that administration of ERMAP can protect DSS-induced colitis in mice by regulating T cell and macrophage functions. This study adds to the evidence for various mechanistic pathways associated to the pathogenesis of IBD, which could subsequently be translated to novel therapeutics.
Insights
Erythrocyte membrane-associated protein (ERMAP) administration protects against dextran sodium sulfate (DSS)-induced colitis in mice by promoting anti-inflammatory M2 macrophages and suppressing T cell responses, offering potential new therapies for inflammatory bowel disease (IBD).
Area of Science:
- Immunology
- Gastroenterology
- Molecular Biology
Background:
- Macrophages and T cells are key players in inflammatory bowel disease (IBD) pathogenesis.
- Erythrocyte membrane-associated protein (ERMAP) is a novel immune checkpoint molecule influencing macrophage polarization and T cell responses.
Purpose of the Study:
- To investigate the therapeutic potential of ERMAP in dextran sodium sulfate (DSS)-induced colitis.
- To elucidate the mechanisms by which ERMAP modulates immune cell function in colitis.
Main Methods:
- Established a DSS-induced colitis model in C57BL/6 mice treated with ERMAP-Fc fusion protein.
- Assessed colitis severity using disease activity index, weight loss, colon length, and histological analysis.
- Utilized flow cytometry, Q-PCR, WB, ELISA, and RNA-seq to analyze immune cell populations, gene expression, and signaling pathways.
Main Results:
- ERMAP administration increased M2 macrophage polarization and suppressed T cell activation and proliferation in DSS colitis.
- ERMAP knockdown in macrophages reduced M2 polarization and enhanced T cell responses.
- Adoptive transfer of ERMAP-deficient macrophages exacerbated colitis, and ERMAP inhibited the NLR pathway in macrophages.
Conclusions:
- ERMAP administration confers protection against DSS-induced colitis by modulating macrophage and T cell functions.
- These findings highlight ERMAP's therapeutic potential for IBD and elucidate its role in immune regulation.
