We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The UDP-glucose/P2Y14 receptor axis promotes eosinophil-dependent large intestinal inflammation.
- Authors
Liu, Li; Ito, Takayoshi; Li, Bo; Tani, Haruka; Okuzaki, Daisuke; Motooka, Daisuke; Miyazaki, Hazuki; Ogino, Takayuki; Nakamura, Shota; Takeda, Kiyoshi; Kayama, Hisako
- Abstract
Ulcerative colitis (UC) is a chronic disorder of the large intestine with inflammation and ulceration. The incidence and prevalence of UC have been rapidly increasing worldwide, but its etiology remains unknown. In patients with UC, the accumulation of eosinophils in the large intestinal mucosa is associated with increased disease activity. However, the molecular mechanism underlying the promotion of intestinal eosinophilia in patients with UC remains poorly understood. Here, we show that uridine diphosphate (UDP)-glucose mediates the eosinophil-dependent promotion of colonic inflammation via the purinergic receptor P2Y14. The expression of P2RY14 mRNA was upregulated in the large intestinal mucosa of patients with UC. The P2Y14 receptor ligand UDP-glucose was increased in the large intestinal tissue of mice administered dextran sodium sulfate (DSS). In addition, P2ry14 deficiency and P2Y14 receptor blockade mitigated DSS-induced colitis. Among the large intestinal immune cells and epithelial cells, eosinophils highly expressed P2ry14 mRNA. P2ry14 −/− mice transplanted with wild-type bone marrow eosinophils developed more severe DSS-induced colitis compared with P2ry14 −/− mice that received P2ry14 -deficient eosinophils. UDP-glucose prolonged the lifespan of eosinophils and promoted gene transcription in the cells through P2Y14 receptor-mediated activation of ERK1/2 signaling. Thus, the UDP-glucose/P2Y14 receptor axis aggravates large intestinal inflammation by accelerating the accumulation and activation of eosinophils.
- Subjects
INFLAMMATORY bowel diseases; ULCERATIVE colitis; LARGE intestine; URIDINE diphosphate; INTESTINES
- Publication
International Immunology, 2024, Vol 36, Issue 4, p155
- ISSN
0953-8178
- Publication type
Article
- DOI
10.1093/intimm/dxad050