Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells

被引：606

作者：

Pallotta, Maria T. ^{[1
]}

Orabona, Ciriana ^{[1
]}

Volpi, Claudia ^{[1
]}

Vacca, Carmine ^{[1
]}

Belladonna, Maria L. ^{[1
]}

Bianchi, Roberta ^{[1
]}

Servillo, Giuseppe ^{[2
]}

Brunacci, Cinzia ^{[2
]}

Calvitti, Mario ^{[1
]}

Bicciato, Silvio ^{[3
]}

Mazza, Emilia M. C. ^{[3
]}

Boon, Louis ^{[4
]}

Grassi, Fabio ^{[5
]}

Fioretti, Maria C. ^{[1
]}

Fallarino, Francesca ^{[1
]}

Puccetti, Paolo ^{[1
]}

Grohmann, Ursula ^{[1
]}

机构：

[1] Univ Perugia, Dept Expt Med & Biochem Sci, I-06100 Perugia, Italy

[2] Univ Perugia, Dept Clin & Expt Med, I-06100 Perugia, Italy

[3] Univ Modena, Dept Biomed Sci, I-41100 Modena, Italy

[4] Bioceros, Utrecht, Netherlands

[5] Biomed Res Inst, Bellinzona, Switzerland

来源：

NATURE IMMUNOLOGY | 2011年 / 12卷 / 09期

关键词：

TRYPTOPHAN CATABOLISM; PROTEASOMAL DEGRADATION; CUTTING EDGE; IDO; INTERFERON; SOCS3; INHIBITION; EXPRESSION; INSIGHTS; RECEPTOR;

D O I：

10.1038/ni.2077

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Regulation of tryptophan metabolism by indoleamine 2,3-dioxygenase (IDO) in dendritic cells (DCs) is a highly versatile modulator of immunity. In inflammation, interferon-gamma is the main inducer of IDO for the prevention of hyperinflammatory responses, yet IDO is also responsible for self-tolerance effects in the longer term. Here we show that treatment of mouse plasmacytoid DCs (pDCs) with transforming growth factor-beta (TGF-beta) conferred regulatory effects on IDO that were mechanistically separable from its enzymic activity. We found that IDO was involved in intracellular signaling events responsible for the self-amplification and maintenance of a stably regulatory phenotype in pDCs. Thus, IDO has a tonic, nonenzymic function that contributes to TGF-beta-driven tolerance in noninflammatory contexts.

引用

页码：870 / U91

页数：11

共 50 条

[1]

Identification of key cytosolic kinases containing evolutionarily conserved kinase tyrosine-based inhibitory motifs (KTIMs) [J].