Inhibition of indoleamine 2,3-dioxygenase 1 expression alters immune response in colon tumor microenvironment in mice.
Bottom Line: Indoleamine 2,3-dioxygenase (IDO), an enzyme that degrades the essential amino acid l-tryptophan along the kynurenine pathway, exerts immunomodulatory effects in a number of diseases.Ido1 deficiency did not lead to significant differences in the size and number of colon tumors.Importantly, 1-mT treatment also significantly altered cytokine expression in the colon tumor tissues.
Affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.Show MeSH
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Mentions: IDO is mainly expressed in the dendritic cells in tumor stroma and tumor draining lymph nodes where it suppresses immune reactions. In the present study, IDO-expressing dendritic cells were also observed in tumor stroma in mouse colon tumors (Fig.1a, inset in the lower right panel and Fig. S1). Therefore, to investigate the effect of IDO1 deficiency on the production of pro-inflammatory and anti-inflammatory cytokines, we examined the mRNA expression levels of Ifng, Tnf, Il-10 and Tgfb in the mouse colon tumor tissue. In both ApcMin/+ and AOM/DSS-treated mice, the expression of Ifng in the colon tumor tissue was significantly higher in Ido1(−/−) mice than in Ido1(+/+) mice (Fig.3a,b). Ido1 deficiency also led to a significantly higher expression of Tnf in the colon tumors of ApcMin/+ mice (Fig.3a), while no significant difference was observed between mice with the Ido1(−/−) and Ido1(+/+) genotypes in AOM/DSS-treated mice (Fig.3b). In contrast, there were no significant differences in the expression of Il-10 and Tgfb between mice with the two genotypes in both ApcMin/+ and AOM/DSS-treated mice (Fig.3a,b). These results indicate that IDO1 alters the expression of pro-inflammatory cytokines in colon tumor tissue. In addition, Ido2 expression was detected in mouse colon tumor tissues, similar to that reported in human CRC;26 however, no significant difference was observed between mice with the Ido1(−/−) and Ido1(+/+) genotypes (Fig.3a,b).
Affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.