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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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-08-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-025-03513-4 |
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| Summary: | 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. |
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| ISSN: | 1742-2094 |