title: Tolerogenic dendritic cells generated with IL-10/TGFβ1 relieve immune thrombocytopenia in mice.
abstract: Activated platelet-specific autoreactive T cells play a key role in the pathophysiology of immune thrombocytopenia (ITP). Tolerogenic dendritic cells (tDCs) that induce T cells tolerance to platelet autoantigens are a promising strategy for specific cellular therapy in autoimmunity. In this study, we generated three kinds of GPIIb-specific tDCs stimulated by IL-10 (10-DCs), TGFβ1 (T-DCs), or a combination of IL-10 and TGFβ1 (10T-DCs), respectively, and compared their phenotypes and biological function. Our data demonstrate that GPIIb-specific 10T-DCs induced the weakest memory lymphocytes responses and exhibited stronger tolerogenic potential than others, making them suitable for tolerance inducing therapies. Furthermore, in ITP mice model we found that 10T-DCs abrogated the decrease in platelet counts and the increase in serum IFN-γ level, confirming the in vivo tolerogenic potential of 10T-DCs. Our study provides a promising strategy for ITP intervention in the clinic by the induction of platelet-specific immune tolerance.
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, 107# Wenhua Xi Road, Jinan, 250012, PR China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Zhang
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Fu
authors.forename: Bin
authors.initials: B
authors.lastname: Ning
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Nianzheng
authors.initials: N
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Jianlu
authors.initials: J
authors.lastname: Wei
authors.forename: Xiuli
authors.initials: X
authors.lastname: Ju
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000276:immunology; D064987:Cell- and Tissue-Based Therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology; D051381:Rats; D013921:Thrombocytopenia / Q000276:immunology / Q000628:therapy*; D053773:Transforming Growth Factor beta1 / Q000276:immunology*
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex; D053773:Transforming Growth Factor beta1; C032193:glycoprotein receptor GPIb-IX; D016753:Interleukin-10
keywords: IL-10; Immune thrombocytopenia; Platelet; TGFβ1; Tolerogenic dendritic cells