title: Decreased indoleamine 2,3-dioxygenase expression in dendritic cells and role of indoleamine 2,3-dioxygenase-expressing dendritic cells in immune thrombocytopenia.
abstract: Indoleamine 2,3-dioxygenase (IDO) expression in dendritic cells (DCs) can induce or maintain peripheral immune tolerance. Impaired IDO-mediated tryptophan catabolism has been observed in autoimmune diseases. In order to investigate the effects of IDO-mediated tryptophan catabolism and IDO-expressing DCs in immune thrombocytopenia, the concentrations of kynurenine were detected by high-pressure liquid chromatography. The expressions of IDO were analyzed by flow cytometry and western blot analysis. The effects of IDO(+) DCs stimulated with CTLA-4-Ig on T cells proliferation and activation, lymphocyte apoptosis, and Tregs were measured by flow cytometry. We found that the expression of IDO in DCs of immune thrombocytopenia (ITP) patients was significantly decreased. CTLA-4-Ig significantly increased the expression of functional IDO in DCs of ITP patients. IDO(+) DCs stimulated with CTLA-4-Ig suppressed T cells proliferation and activation, promoted lymphocyte apoptosis, and increased the percentage of Tregs. These results suggest that decreased IDO expression in DCs may play a critical role in ITP. CTLA-4-Ig successfully corrected the disorder of IDO expression in ITP. IDO(+) DCs stimulated with CTLA-4-Ig inhibited immune responses by an IDO-dependent mechanism. Increasing the expression and activity of IDO in DCs might be a promising therapeutic approach for ITP.
authors.affiliation: Hematology Oncology Centre, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, China.
authors.forename: Shu-qian
authors.initials: SQ
authors.lastname: Xu
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Wang
authors.forename: Xiao-juan
authors.initials: XJ
authors.lastname: Zhu
authors.forename: Xiao-yuan
authors.initials: XY
authors.lastname: Dong
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.forename: Ping
authors.initials: P
authors.lastname: Qin
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Sun
authors.forename: Chengshan
authors.initials: C
authors.lastname: Guo
authors.forename: Heyu
authors.initials: H
authors.lastname: Ni
authors.forename: Ming
authors.initials: M
authors.lastname: Hou
mesh_terms: D000293:Adolescent; D000328:Adult; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology*; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013921:Thrombocytopenia / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase