ReferenceID 2287
Mannose metabolism normalizes gut homeostasis by blocking the TNF-α-mediated proinflammatory circuit
Cell Mol Immunol
Mannose is a naturally occurring sugar widely consumed in the daily diet; however, mechanistic insights into how mannose metabolism affects intestinal inflammation remain lacking. Herein, we reported that mannose supplem
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Record Fields
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- Reference Id
- 2287
- Evidence Id
- 18877
- Core Evidence Id
- 18877
- Source Reference Id
- 4598
- Herb2 Reference Id
- HBREF005395
- Subject Paper Key
- HBIN034421_36471112
- Pubmed Id
- 36471112
- Doi
- 10.1038/s41423-022-00955-1
- Paper Title
- Mannose metabolism normalizes gut homeostasis by blocking the TNF-α-mediated proinflammatory circuit
- Paper Abstract
- Mannose is a naturally occurring sugar widely consumed in the daily diet; however, mechanistic insights into how mannose metabolism affects intestinal inflammation remain lacking. Herein, we reported that mannose supplementation ameliorated colitis development and promoted colitis recovery. Macrophage-secreted inflammatory cytokines, particularly TNF-α, induced pathological endoplasmic reticulum stress (ERS) in intestinal epithelial cells (IECs), which was prevented by mannose via normalization of protein N-glycosylation. By preserving epithelial integrity, mannose reduced the inflammatory activation of colonic macrophages. On the other hand, mannose directly suppressed macrophage TNF-α production translationally by reducing the glyceraldehyde 3-phosphate level, thus promoting GAPDH binding to TNF-α mRNA. Additionally, we found dysregulated mannose metabolism in the colonic mucosa of patients with inflammatory bowel disease. Finally, we revealed that activating PMM2 activity with epalrestat, a clinically approved drug for the treatment of diabetic neuropathy, elicited further sensitization to the therapeutic effect of mannose. Therefore, mannose metabolism prevents TNF-α-mediated pathogenic crosstalk between IECs and intestinal macrophages, thereby normalizing aberrant immunometabolism in the gut.
- Journal
- Cell Mol Immunol
- Publish Year
- 2022
- Experiment Subject
- patient
- Experiment Type
- Cell Experiment
- Phenotype Related
- Diabetic Neuropathy; Colitis; Inflammatory Bowel Disease; Intestinal Inflammation
- Paper Title Cn
- Paper Title En
- Mannose metabolism normalizes gut homeostasis by blocking the TNF-α-mediated proinflammatory circuit
- Bilingual Status
- semi_complete