title: CD103 marks a subset of human CD34+-derived langerin+ dendritic cells that induce T-regulatory cells via indoleamine 2,3-dioxygenase-1.
abstract: Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive molecule expressed in some subsets of normal and neoplastic cells. Mature human dendritic cells (DCs) have been shown to express IDO1, but little is known about its expression and function during DC differentiation from bone marrow hematopoietic stem/progenitor cells (HSPCs). Here, we show that during in vitro differentiation along the myeloid DC lineage, CD34(+) HSPCs acquire IDO1 expression, which acts in a tolerogenic manner by inducing a population of fully functional CD4(+)CD25(+) FOXP3(+) T-regulatory cells. Phenotypically, CD1a(+)CD14(-) HPSC-derived DCs expressed IDO1, langerin, CD11b, and CD1c. Cell-sorting experiments demonstrated that IDO1 expression is found in a subset of CD1a(+)CD14(-)langerin(+) cells, expressing CD103, which is capable of inducing T-regulatory cells in an IDO1-dependent manner. In conclusion, DC differentiation from CD34(+) HSPCs results in the expression of a functionally active IDO1 protein in CD1a(+)langerin(+), CD103-expressing DCs. These data point toward IDO1 expression as part of a tolerogenic signature during DC development.
authors.affiliation: Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology "Seràgnoli", University of Bologna, Bologna, Italy.
authors.forename: Darina
authors.initials: D
authors.lastname: Očadlíková
authors.affiliation: Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology "Seràgnoli", University of Bologna, Bologna, Italy; Ludwig Center for Cancer Research of the University of Lausanne, Lausanne, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Trabanelli
authors.affiliation: Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology "Seràgnoli", University of Bologna, Bologna, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Salvestrini
authors.affiliation: Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology "Seràgnoli", University of Bologna, Bologna, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Ciciarello
authors.affiliation: Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology "Seràgnoli", University of Bologna, Bologna, Italy; Dipartimento di Scienze Biomediche e Neuromotorie, University of Bologna, Bologna, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Evangelisti
authors.affiliation: Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology "Seràgnoli", University of Bologna, Bologna, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Lecciso
authors.affiliation: Hematopathology and Hematology Sections, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Sabattini
authors.affiliation: Hematopathology and Hematology Sections, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Righi
authors.affiliation: Hematopathology and Hematology Sections, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Piccioli
authors.affiliation: Hematopathology and Hematology Sections, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.affiliation: Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology "Seràgnoli", University of Bologna, Bologna, Italy; Chair of Hematology, University of Genoa, Istituto Nazionale per la Ricerca Sul Cancro Azienda Ospedaliera Universitaria S. Martino-IST, Genoa, Italy.
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Lemoli
authors.affiliation: Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology "Seràgnoli", University of Bologna, Bologna, Italy. Electronic address: antonio.curti2@unibo.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Curti
mesh_terms: D015703:Antigens, CD / Q000276:immunology*; D018952:Antigens, CD34 / Q000276:immunology*; D015153:Blotting, Western; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D039001:Integrin alpha Chains / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology*; D037241:Mannose-Binding Lectins / Q000276:immunology*; D008856:Microscopy, Fluorescence; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; C121916:CD207 protein, human; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D039001:Integrin alpha Chains; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; C091367:alpha E integrins