IDO2, much mopre than a clone of IDO1 : un veiling a new biological role for an ancient enzyme 

Ente finanziatore: MIUR

Unità di Ricerca:  Unita 2 Responsabile  Lello Zolla

Responsabile scientifico: Claudia Volpi. Universita Perugia

Partecipanti:  Zolla Lello, Federica Gevi e Giuseppina Fanelli

Durata (data di inizio/data di fine): 05/02/2017 - 04/06/2020

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 immunometabolism and that their joint modulation could represent an important target for effective immunotherapy in several disease settings. A comparison with ancestral IDO2 will carry out in order to discover the improvemnts rrched durin evolution.