Tolerogenic dendritic cells generated with IL-10/TGFβ1 relieve immune thrombocytopenia in mice

摘要

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 (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-γlevel, 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.