CRTH2 is critical for IL-1β-producing B cells during experimental autoimmune encephalomyelitis in mice via p38 signaling
Abstract B cells play a critical role in the pathogenesis of autoimmune inflammatory diseases such as multiple sclerosis (MS). As a receptor of prostaglandin D2, chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2) is known to be involved in Th2 cell activation, but its functi...
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| Format: | Article |
| Language: | English |
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BMC
2025-08-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-025-03513-4 |
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| author | Jiao Liu Bei Wang Chunyan Wu Ting Wang Jie Zhou Yujun Shen Ying Yu Shengkai Zuo |
| author_facet | Jiao Liu Bei Wang Chunyan Wu Ting Wang Jie Zhou Yujun Shen Ying Yu Shengkai Zuo |
| author_sort | Jiao Liu |
| collection | DOAJ |
| description | Abstract B cells play a critical role in the pathogenesis of autoimmune inflammatory diseases such as multiple sclerosis (MS). As a receptor of prostaglandin D2, chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2) is known to be involved in Th2 cell activation, but its function in B lymphocytes is unclear. Here, we show that CRTH2 is critical for an IL-1β-producing B cell subset. Mice with B-cell-specific deletion of Crth2 exhibit reduced numbers of IL-1β-producing B cells, resulting in amelioration of experimental autoimmune encephalomyelitis (EAE), the principal animal model of MS. Compared to wild-type B cells, adoptive transfer of Crth2-deficient B cells attenuates EAE disease severity in B-cell-deficient recipient mice. The IL-1β-producing B cell subpopulation was mainly transitional type 2 B cells identified by flow cytometry and single cell sequencing. Mechanically, CRTH2 promotes IL-1β production in B cells through p38 signaling, and pharmacological inhibition of p38 attenuates EAE disease severity in DK-PGD2-treated mice. Taken together, our results reveal a key function of CRTH2 in driving IL-1β expression in B cells and in controlling their pathogenic activity in autoimmune diseases. |
| format | Article |
| id | doaj-art-e6df9e3e851d448e85007cd01a18e4a0 |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-e6df9e3e851d448e85007cd01a18e4a02025-08-20T03:46:12ZengBMCJournal of Neuroinflammation1742-20942025-08-0122111710.1186/s12974-025-03513-4CRTH2 is critical for IL-1β-producing B cells during experimental autoimmune encephalomyelitis in mice via p38 signalingJiao Liu0Bei Wang1Chunyan Wu2Ting Wang3Jie Zhou4Yujun Shen5Ying Yu6Shengkai Zuo7Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, State Key Laboratory of Experimental Hematology, School of Basic Medical Sciences, Tianjin Medical UniversityDepartment of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, State Key Laboratory of Experimental Hematology, School of Basic Medical Sciences, Tianjin Medical UniversityDepartment of Biopharmaceutics, School of Pharmacy, Tianjin Medical UniversityDepartment of Biopharmaceutics, School of Pharmacy, Tianjin Medical UniversityDepartment of Immunology, School of Basic Medical Sciences, Tianjin Medical UniversityDepartment of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, State Key Laboratory of Experimental Hematology, School of Basic Medical Sciences, Tianjin Medical UniversityDepartment of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, State Key Laboratory of Experimental Hematology, School of Basic Medical Sciences, Tianjin Medical UniversityDepartment of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, Center for Cardiovascular Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, State Key Laboratory of Experimental Hematology, School of Basic Medical Sciences, Tianjin Medical UniversityAbstract B cells play a critical role in the pathogenesis of autoimmune inflammatory diseases such as multiple sclerosis (MS). As a receptor of prostaglandin D2, chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2) is known to be involved in Th2 cell activation, but its function in B lymphocytes is unclear. Here, we show that CRTH2 is critical for an IL-1β-producing B cell subset. Mice with B-cell-specific deletion of Crth2 exhibit reduced numbers of IL-1β-producing B cells, resulting in amelioration of experimental autoimmune encephalomyelitis (EAE), the principal animal model of MS. Compared to wild-type B cells, adoptive transfer of Crth2-deficient B cells attenuates EAE disease severity in B-cell-deficient recipient mice. The IL-1β-producing B cell subpopulation was mainly transitional type 2 B cells identified by flow cytometry and single cell sequencing. Mechanically, CRTH2 promotes IL-1β production in B cells through p38 signaling, and pharmacological inhibition of p38 attenuates EAE disease severity in DK-PGD2-treated mice. Taken together, our results reveal a key function of CRTH2 in driving IL-1β expression in B cells and in controlling their pathogenic activity in autoimmune diseases.https://doi.org/10.1186/s12974-025-03513-4CRTH2B cellsIL-1βExperimental autoimmune encephalomyelitisp38 MAPK signaling |
| spellingShingle | Jiao Liu Bei Wang Chunyan Wu Ting Wang Jie Zhou Yujun Shen Ying Yu Shengkai Zuo CRTH2 is critical for IL-1β-producing B cells during experimental autoimmune encephalomyelitis in mice via p38 signaling Journal of Neuroinflammation CRTH2 B cells IL-1β Experimental autoimmune encephalomyelitis p38 MAPK signaling |
| title | CRTH2 is critical for IL-1β-producing B cells during experimental autoimmune encephalomyelitis in mice via p38 signaling |
| title_full | CRTH2 is critical for IL-1β-producing B cells during experimental autoimmune encephalomyelitis in mice via p38 signaling |
| title_fullStr | CRTH2 is critical for IL-1β-producing B cells during experimental autoimmune encephalomyelitis in mice via p38 signaling |
| title_full_unstemmed | CRTH2 is critical for IL-1β-producing B cells during experimental autoimmune encephalomyelitis in mice via p38 signaling |
| title_short | CRTH2 is critical for IL-1β-producing B cells during experimental autoimmune encephalomyelitis in mice via p38 signaling |
| title_sort | crth2 is critical for il 1β producing b cells during experimental autoimmune encephalomyelitis in mice via p38 signaling |
| topic | CRTH2 B cells IL-1β Experimental autoimmune encephalomyelitis p38 MAPK signaling |
| url | https://doi.org/10.1186/s12974-025-03513-4 |
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