| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2022: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2021: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Outline of Final Research Achievements |
Although the incidence and prevalence of ulcerative colitis (UC) and Crohn's disease (CD) are increasing globally, their etiology remains poorly understood. To define the impacts of interactions between intestinal metabolites and immune cells through GPCRs on the pathogenesis of UC and CD, we have conducted the following studies: (1) The influence of LysoPS in progression of CD: We identified that LysoPS derived from dysbiotic microbiota enhances Th1 responses through P2Y10 receptor and exaggerate colitis. (2) The influence of UDP-glucose-P2Y10 receptor signaling in UC aggravation: We identified that P2RY14 mRNA is highly expressed in colonic mucosa from UC patients and its ligand UDP-glucose is increased in inflamed sites of colonic mucosa. We demonstrated that activation of UDP-glucose-P2Y10 receptor signaling leads to prolonged survival of colonic eosinophils by inducing phosphorylation of ERK1/2 and thereby aggravates dextran sodium sulfate-induced colitis.
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