title: Decreased expression of indoleamine 2,3-dioxygenase 1 in dendritic cells contributes to impaired regulatory T cell development in immune thrombocytopenia.
abstract: Along with their immunogenic role, dendritic cells (DCs) are also critical in maintaining tolerance to self-antigens by inducing regulatory T cells (Tregs) via the expression of the immunomodulatory enzyme indoleamine 2,3-dioxygenase 1 (IDO1). In turn, Tregs modulate the maturation and/or function of DCs. In immune thrombocytopenia (ITP), the interaction between DCs and Tregs has never been investigated although decreased number/function of Tregs as well as altered DCs have been described. Here, we ask whether, in ITP: (1) IDO1 expression/activity is decreased in mature DCs; (2) IDO1-mediated Treg generation is impaired; and (3) DC maturation is abnormally modulated by Tregs. We found that in ITP, DCs show reduced capability of upregulating the expression/activity of IDO1. This finding results in the reduced ability of mature DCs of converting T cells into Tregs. In turn, Tregs are characterized by decreased interleukin-10 production and show lower ability of inhibiting DC maturation. In conclusion, these data point out the role of IDO1 in the impaired regulatory T cell development of ITP patients and suggest that the cross-talk between Tregs and DCs is hampered and plays a pathogenetic role.
authors.affiliation: Institute of Hematology, Department of Hematology and Oncological Sciences L. e A. Seràgnoli, University of Bologna, Bologna, Italy. lucia.catani@unibo.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Catani
authors.forename: Daria
authors.initials: D
authors.lastname: Sollazzo
authors.forename: Sara
authors.initials: S
authors.lastname: Trabanelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Curti
authors.forename: Cecilia
authors.initials: C
authors.lastname: Evangelisti
authors.forename: Nicola
authors.initials: N
authors.lastname: Polverelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Palandri
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Nicola
authors.initials: N
authors.lastname: Vianelli
authors.forename: Roberto Massimo
authors.initials: RM
authors.lastname: Lemoli
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D002454:Cell Differentiation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000201:enzymology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis* / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000473:pathology*; D015854:Up-Regulation
chemical_list: C576710:IDO1 protein, human; C508609:IL10 protein, human; C508017:IL2RA protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D016753:Interleukin-10