Tolerogenic dendritic cells generated with IL-10/TGF¦Â1 relieve immune thrombocytopenia in mice

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• 作者：Aijun Zhang ; Jinqiu Fu ; Bin Ning ; Dong Li ; Nianzheng Sun ; Wei Wei ; Jianlu Wei ; Xiuli Ju
• 关键词：Immune thrombocytopenia ; Tolerogenic dendritic cells ; Platelet ; IL-10 ; TGF¦Â1
• 刊名：Thrombosis Research
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：132
• 期：1
• 页码：63-68
• 全文大小：794 K

文摘

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), TGF¦Â1 (T-DCs), or a combination of IL-10 and TGF¦Â1 (10 T-DCs), respectively, and compared their phenotypes and biological function. Our data demonstrate that GPIIb-specific 10 T-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 10 T-DCs abrogated the decrease in platelet counts and the increase in serum IFN-¦Ãlevel, confirming the in vivo tolerogenic potential of 10 T-DCs. Our study provides a promising strategy for ITP intervention in the clinic by the induction of platelet-specific immune tolerance.