Indoleamine 2,3-dioxygenase activity contributes to local immune suppression in the skin expressing human papillomavirus oncoprotein e7.

ABSTRACT: Chronic infection of anogenital epithelium with human papillomavirus (HPV) promotes development of cancer. Many pathogens evoke immunosuppressive mechanisms to enable persistent infection. We have previously shown that grafted skin expressing HPV16 E7 oncoprotein from a keratin-14 promoter (K14E7) is not rejected by a syngeneic, immunocompetent host. In this study we show that indoleamine 2,3-dioxygenase (IDO) 1, an IFN-γ-inducible immunoregulatory molecule, is more highly expressed by langerin(-ve) dermal dendritic cells (DCs) from K14E7 skin than nontransgenic control skin. Furthermore, inhibiting IDO activity using 1-methyl-dl-tryptophan (1-D/L-MT) promotes K14E7 skin graft rejection. Increased IDO1 expression and activity in K14E7 skin requires IFN-γ and invariant natural killer T (iNK

SUBMITTER: Mittal D 

PROVIDER: S-EPMC3779505 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature