A Relay Pathway between Arginine and Tryptophan Metabolism Confers Immunosuppressive Properties on Dendritic Cells

作者：Mondanelli Giada; Bianchi Roberta; Pallotta Maria Teresa; Orabona Ciriana; Albini Elisa; Iacono Alberta; Belladonna Maria Laura; Vacca Carmine; Fallarino Francesca; Macchiarulo Antonio; Ugel Stefano; Bronte Vincenzo; Gevi Federica; Zolla Lello; Verhaar Auke; Peppelenbosch Maikel; Mazza Emilia Maria Cristina; Bicciato Silvio; Laouar Yasmina; Santambrogio Laura; Puccetti Paolo; Volpi Claudia^*; Grohmann Ursula^*

来源：Immunity, 2017, 46(2): 233-244.

DOI：10.1016/j.immuni.2017.01.005

Arginase 1 (Arg1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunoregulatory enzymes catalyzing the degradation of L-arginine and L-tryptophan, respectively, resulting in local amino acid deprivation. In addition, unlike Arg1, IDO1 is also endowed with non-enzymatic signaling activity in dendritic cells (DCs). Despite considerable knowledge of their individual biology, no integrated functions of Arg1 and IDO1 have been reported yet. We found that IDO1 phosphorylation and consequent activation of IDO1 signaling in DCs was strictly dependent on prior expression of Arg1 and Arg1-dependent production of polyamines. Polyamines, either produced by DCs or released by bystander Arg1(+) myeloid-derived suppressor cells, conditioned DCs toward an IDO1-dependent, immunosuppressive phenotype via activation of the Src kinase, which has IDO1-phosphorylating activity. Thus our data indicate that Arg1 and IDO1 are linked by an entwined pathway in immuno-metabolism and that their joint modulation could represent an important target for effective immunotherapy in several disease settings.

• 出版日期2017-2-21
• 单位Perugia