CRTH2 is critical for IL-1β-producing B cells during experimental autoimmune encephalomyelitis in mice via p38...

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.