Table 1.
Implication of tryptophan/kynurenine pathway in the survival of heart transplantation.
| Author | Human/animal | Method | Findings |
|---|---|---|---|
| Suarez-Fuentetaja et al 158 | Human | An observational study measuring serum IDO activity in patients with heart transplantation | Patients with acute rejection had higher IDO serum activity after 1 month of transplantation. Also, IDO serum activity independently (95% CI, OR 1.4 [1.033-1.876]) predicted graft rejection among patients with heart transplantation |
| Li et al 164 | Mouse | Treating animals with dendritic cells transfected with adenovirus vector carrying IDO gene | IDO overexpression improved survival, postponed graft rejection, reduced IFN-γ production, and accelerated CD4+ cell death |
| He et al 162 | Rat | Treating animals with bone marrow stem cells transfected with lentiviral vector carrying IDO gene | IDO overexpression prolonged survival, enhanced ejection fraction, decreased CD86+, CD80+ cells, MHC II, IL2 and IFN-γ and increased T Reg cells abundance and the expression of CD274, IL10, TGF-β1, TGF-β2, TGF-β3 in the heart allograft |
| Yang et al 159 | Rat | Treating rats with immutol, cyclosporine and 1-MT | 1-MT significantly blocked kynurenine pathway and decreased graft survival. Activation of kynurenine pathway has been associated with increased abundance of T Reg cells, higher concentrations of IL10, and TGF-β, as well as decreased abundance of CD8+ cells |
| Dai et al 171 | Rat | A single-dose intravenous administration of 3-hydroxyanthranilic acid + allogeneic dendritic cells 7 days before heart transplantation | Pretreatment with the combination of 3-hydroxyanthranilic acid + allogeneic dendritic cells enhanced cardiac allograft survival and suppressed T cells activity |
| Lv et al 161 | Mouse | Treating mice with dendritic cells transfected with adenovirus vector carrying IDO gene | IDO overexpression enhanced both cardiac graft survival and function. Higher IL10/IL6 ratio and lower levels of IFN-γ and IL-2 were found in treated group |
| Li et al 170 | Mouse | Transferring tolerogenic dendritic cells from a tolerant recipient to secondary recipient in mice heart transplantation model | Tolerogenic dendritic cells transfer from a tolerant recipient to another recipient significantly enhanced IDO expression, induced T Reg differentiation, suppressed anti-donor T cells activity and increased graft survival in the secondary recipient |
| Li et al 172 | Mouse | Treating mice with intravenous injection of tryptophan catabolic metabolites, dendritic cells transfected with adenovirus vector carrying IDO gene and their combination | Treating mice with tryptophan catabolic metabolites or adenoviral transfected dendritic cells significantly increased cardiac graft survival, decreased IL2, TNF-α and IFN-γ and increased IL10. Significantly greater improvement was observed in combination therapy |
| Yu et al 169 | Mouse | Cardiac allograft injection with adenovirus vector carrying IDO gene. | Higher IDO expression was detected in treated mice. Increased IDO expression was associated with decreased expression of IL2, IL17, and IFN-γ. IDO enhanced T Reg cells differentiation and prolonged graft survival |
| He et al 166 | Rat | Intravenous injection of DO1-BMSC-exosomes 48 h after heart transplantation | Treated rats showed better cardiac function. Treatment with DO1-BMSC-exosomes augmented T Reg response and suppressed CD8+ response |
| Li et al 176 | Mouse | Measuring microRNAs in mice cardiac transplantation and assessing their effect on cardiac allograft rejection and IDO expression | miR-669b-3p decreased IDO expression, thereby expediting graft rejection |
| Sucher et al 167 | Mouse | Treating heart transplanted mice with cytotoxic T lymphocyte-associated antigen-4 Ig (CTLA4Ig) | CTLA4Ig promoted IDO expression, thereby increasing graft survival. IDO gene deletion accelerated graft rejection. Furthermore, IDO inhibition since transplantation or 50 days after transplantation attenuated the beneficial effects of CTLA4Ig on graft survival. In addition, T Reg cells depletion impairs CTLA4Ig-mediated graft survival |
| Zhang et al 165 | Mouse | Intravenous injection of dendritic cells transfected with adenovirus vector carrying GDF15 gene 7 days before transplantation | GDF15 overexpression upregulated IDO in dendritic cells, thereby inducing tolerance in T cells and delaying graft rejection |