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 Relay Pathway between Arginine and Tryptophan Metabolism Confers Immunosuppressive Properties on Dendritic Cells / 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. - In: IMMUNITY. - ISSN 1074-7613. - 46:2(2017), pp. 233-244. [10.1016/j.immuni.2017.01.005]

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

BIANCHI, Roberta;BRONTE, VINCENZO;MAZZA, Emilia Maria Cristina;BICCIATO, Silvio;
2017

Abstract

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.
2017
14-feb-2017
46
2
233
244
A Relay Pathway between Arginine and Tryptophan Metabolism Confers Immunosuppressive Properties on Dendritic Cells / 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. - In: IMMUNITY. - ISSN 1074-7613. - 46:2(2017), pp. 233-244. [10.1016/j.immuni.2017.01.005]
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
File in questo prodotto:
File Dimensione Formato  
Mondanelli_et_al_Immunity_2017.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 1.91 MB
Formato Adobe PDF
1.91 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1134646
Citazioni
  • ???jsp.display-item.citation.pmc??? 110
  • Scopus 217
  • ???jsp.display-item.citation.isi??? 210
social impact