Normal development and function of dendritic cells in mice lacking IDO-1 expression.
Dendritic cells (DCs) have been shown to express the tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO-1), a protein presently thought to exert dual and possibly contrasting effects on the immune response. Depletion of tryptophan and release of tryptophan catabolites have been shown to exert a tolerogenic influence on T cell responses, while the IDO enzymatic activity has been recently suggested to promote DC maturation. In this report, we have explored the putative role of IDO-1 in regulating DC biology by analyzing DC development and function from IDO-1 deficient mice. In keeping with previous observations, lack of IDO-1 expression was found to affect in vitro DC generation from bone mouse precursors cultured in the presence of GM-CSF. However, change in growth factor (Flt3L) and/or culture conditions (low-adherence vessels) abolished the difference observed between wt (wild type) and IDO-1-deficient, in vitro generated DCs. Moreover, IDO-1-deficient mice displayed a normal DC compartment in vivo, suggesting that IDO-1 does not play a significant role in DC development and function in vivo. Collectively, these observations suggest that despite a possible role for IDO-1 expression in regulating DC differentiation in vitro under commonly used culture conditions, IDO-1 is largely dispensable for DC development and function in vivo.
de Faudeur
Geoffroy
G
Laboratoire de Physiologie Animale, Institut de Biologie et Médecine Moléculaire, Université Libre de Bruxelles, Belgium.
de Trez
Carl
C
Muraille
Eric
E
Leo
Oberdan
O
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D015971:Gene Expression Regulation, Enzymologic; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000145:classification / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000145:classification / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010641:Phenotype
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007527:Isoenzymes