ERMAP attenuates DSS-induced colitis in mice by regulating macrophage and T cell functions
Abstract 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 negative...
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BMC
2025-05-01
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| Series: | BMC Gastroenterology |
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| Online Access: | https://doi.org/10.1186/s12876-025-03840-z |
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| author | Lu Xia Yiwen Pan Xianbin Wang Rong Hu Jie Gao Wei Chen Keke He Dongbin Cui Youbo Zhao Lu Liu Laijun Lai Min Su |
| author_facet | Lu Xia Yiwen Pan Xianbin Wang Rong Hu Jie Gao Wei Chen Keke He Dongbin Cui Youbo Zhao Lu Liu Laijun Lai Min Su |
| author_sort | Lu Xia |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-e1e7832e033b42dc92f6fbf662633522 |
| institution | DOAJ |
| issn | 1471-230X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj-art-e1e7832e033b42dc92f6fbf6626335222025-08-20T03:10:20ZengBMCBMC Gastroenterology1471-230X2025-05-0125111410.1186/s12876-025-03840-zERMAP attenuates DSS-induced colitis in mice by regulating macrophage and T cell functionsLu Xia0Yiwen Pan1Xianbin Wang2Rong Hu3Jie Gao4Wei Chen5Keke He6Dongbin Cui7Youbo Zhao8Lu Liu9Laijun Lai10Min Su11Center for Tissue Engineering and Stem Cell Research, Guizhou Medical UniversityDepartment of Histology and Embryology, Guizhou Medical UniversityDepartment of Histology and Embryology, Guizhou Medical UniversityTranslational Medicine Research Center of Guizhou Medical UniversityTranslational Medicine Research Center of Guizhou Medical UniversityDepartment of Histology and Embryology, Guizhou Medical UniversityDepartment of Histology and Embryology, Guizhou Medical UniversityCenter for Tissue Engineering and Stem Cell Research, Guizhou Medical UniversityCenter for Tissue Engineering and Stem Cell Research, Guizhou Medical UniversityThe Public Health Clinical Center of Guiyang CityDepartment of Allied Health Sciences, University of ConnecticutCenter for Tissue Engineering and Stem Cell Research, Guizhou Medical UniversityAbstract 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.https://doi.org/10.1186/s12876-025-03840-zERMAPInflammatory bowel diseaseMacrophagesT cells |
| spellingShingle | Lu Xia Yiwen Pan Xianbin Wang Rong Hu Jie Gao Wei Chen Keke He Dongbin Cui Youbo Zhao Lu Liu Laijun Lai Min Su ERMAP attenuates DSS-induced colitis in mice by regulating macrophage and T cell functions BMC Gastroenterology ERMAP Inflammatory bowel disease Macrophages T cells |
| title | ERMAP attenuates DSS-induced colitis in mice by regulating macrophage and T cell functions |
| title_full | ERMAP attenuates DSS-induced colitis in mice by regulating macrophage and T cell functions |
| title_fullStr | ERMAP attenuates DSS-induced colitis in mice by regulating macrophage and T cell functions |
| title_full_unstemmed | ERMAP attenuates DSS-induced colitis in mice by regulating macrophage and T cell functions |
| title_short | ERMAP attenuates DSS-induced colitis in mice by regulating macrophage and T cell functions |
| title_sort | ermap attenuates dss induced colitis in mice by regulating macrophage and t cell functions |
| topic | ERMAP Inflammatory bowel disease Macrophages T cells |
| url | https://doi.org/10.1186/s12876-025-03840-z |
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