ReferenceID 2941
Taurodeoxycholic acid and valine reverse obesity-associated augmented alloimmune responses and prolong allograft survival
Am J Transplant
Obesity initiates a chronic inflammatory network linked to perioperative complications and increased acute rejection rates in organ transplantation. Bariatric surgery is the most effective treatment of obesity recommende
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- Reference Id
- 2941
- Evidence Id
- 19531
- Core Evidence Id
- 19531
- Source Reference Id
- 5876
- Herb2 Reference Id
- HBREF006673
- Subject Paper Key
- HBIN045589_34551205
- Pubmed Id
- 34551205
- Doi
- 10.1111/ajt.16856
- Paper Title
- Taurodeoxycholic acid and valine reverse obesity-associated augmented alloimmune responses and prolong allograft survival
- Paper Abstract
- Obesity initiates a chronic inflammatory network linked to perioperative complications and increased acute rejection rates in organ transplantation. Bariatric surgery is the most effective treatment of obesity recommended for morbidly obese transplant recipients. Here, we delineated the effects of obesity and bariatric surgery on alloimmunity and transplant outcomes in diet-induced obese (DIO) mice. Allograft survival was significantly shorter in DIO-mice. When performing sleeve gastrectomies (SGx) prior to transplantation, we found attenuated T cell-derived alloimmune responses resulting in prolonged allograft survival. Administering taurodeoxycholic acid (TDCA) and valine, metabolites depleted in DIO-mice and restored through SGx, prolonged graft survival in DIO-mice comparable with SGx an dampened Th1 and Th17 alloimmune responses while Treg frequencies and CD4+ T cell-derived IL-10 production were augmented. Moreover, in recipient animals treated with TDCA/valine, levels of donor-specific antibodies had been reduced. Mechanistically, TDCA/valine restrained inflammatory M1-macrophage polarization through TGR5 that compromised cAMP signaling and inhibited macrophage-derived T cell activation. Consistently, administering a TGR5 agonist to DIO-mice prolonged allograft survival. Overall, we provide novel insights into obesity-induced inflammation and its impact on alloimmunity. Furthermore, we introduce TDCA/valine as a noninvasive alternative treatment for obese transplant patients.
- Journal
- Am J Transplant
- Publish Year
- 2022
- Experiment Subject
- mouse; patient
- Experiment Type
- Animal Experiment
- Phenotype Related
- Diet-induced Obese; Attenuated T; Obesity; Alloimmunity; Sleeve Gastrectomies; Obese
- Paper Title Cn
- Paper Title En
- Taurodeoxycholic acid and valine reverse obesity-associated augmented alloimmune responses and prolong allograft survival
- Bilingual Status
- semi_complete