| First Author | Takamatsu M | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 6 | Pages | 3057-64 |
| PubMed ID | 23956437 | Mgi Jnum | J:205871 |
| Mgi Id | MGI:5546556 | Doi | 10.4049/jimmunol.1203306 |
| Citation | Takamatsu M, et al. (2013) IDO1 plays an immunosuppressive role in 2,4,6-trinitrobenzene sulfate-induced colitis in mice. J Immunol 191(6):3057-64 |
| abstractText | IDO, an enzyme that degrades the essential amino acid L-tryptophan to N-formylkynurenine, is known to exert immunomodulatory effects in a number of diseases and disorders. IDO expression is increased in tumors, where it is thought to be involved in tumor evasion by suppressing the immune response. A competitive inhibitor of IDO is currently being tested in clinical trials for relapsed or refractory solid tumors; however, there remains a concern that attenuation of the immunosuppressive function of IDO might exacerbate inflammatory responses. In this study, we investigated the role of IDO in 2,4,6-trinitrobenzene sulfate (TNBS)-induced colitis in mice by gene deletion and pharmacological inhibition. TNBS treatment induced significantly more severe colitis in Ido1 gene-deficient (Ido1(-)/(-)) mice than in Ido1 wild-type (Ido1(+)/(+)) mice, indicating a role for IDO1 in suppression of acute colitis. Consistent with this, the expression of Ido1 was increased in the colonic interstitial tissues of TNBS-treated Ido1(+)/(+) mice. Furthermore, transplantation of Ido1(+)/(+) bone marrow cells into Ido1(-)/(-) mice reduced the pathological damage associated with colitis, altered the expression of cytokines, including IFN-gamma, TNF-alpha, and IL-10, and increased the number of CD4(+) Foxp3(+) regulatory T cells in the colon. Pharmacological inhibition of IDO enzymatic activity by oral administration of 1-methyltryptophan (1-methyl-L-tryptophan or 1-methyl-D-tryptophan) significantly increased the severity of TNBS-induced colitis in mice, demonstrating that both stereoisomers can promote colitis. Collectively, our data indicate that IDO1 plays an important immunoregulatory role in the colon. |
