Tacrolimus ameliorates thrombocytopenia in an ITP mouse model
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ORIGINAL ARTICLE
Tacrolimus ameliorates thrombocytopenia in an ITP mouse model Xiamin Wang 1,2,3 & Jun Lu 4 & Guangyu Wei 1,2,3 & Huan Tong 1,2,3 & Jingxin Zhou 5 & Yangyang Ding 1,2,3 & Sixuan Zhang 1,2,3 & Xiaoqi Xu 1,2,3 & Ran Lai 6 & Qi Luo 1,2,3 & Wen Ju 1,2,3 & Zhiling Yan 2 & Lingyu Zeng 1,2,3 & Kailin Xu 1,2 & Jianlin Qiao 1,2,3 Received: 15 July 2019 / Accepted: 27 July 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Immune thrombocytopenia (ITP) is an autoimmune disease characterized by lower platelet count resulting from immune cellsmediated platelet clearance. Tacrolimus is an immunosuppressive agent which selectively inhibits T cell activation. Whether tacrolimus plays a role in ITP remains unclear. This study aimed to investigate the effect of tacrolimus on ITP in mice. An ITP mouse model was established by injection of rat anti-mouse integrin GPIIb/CD41 immunoglobulin and treated with tacrolimus followed by isolation of peripheral blood mononuclear cells and plasma. The mRNA expression of T-bet, GATA3, and Foxp3 was measured by RT-PCR, and level of IFN-γ, IL-12p70, IL-4, IL-13, and TGF-β in plasma was measured by ELISA. Tacrolimus inhibited antiplatelet antibody-mediated platelet clearance in ITP mouse model. Meanwhile, tacrolimus-treated ITP mice displayed a significant decrease in the mRNA expression of T-bet and plasma level of IFN-γ and IL-12p70 compared with ITP mice but without differences when compared with normal mice. Furthermore, the expression of GATA3, Foxp3, and plasma level of IL-4 and TGF-β were upregulated in tacrolimus-treated ITP mice without significant differences to normal mice (except TGF-β). Tacrolimus prevents antiplatelet antibody-mediated thrombocytopenia in ITP mice possibly through regulating T cell differentiations, suggesting it might be a novel approach for preventing ITP. Keywords Tacrolimus . Immune thrombocytopenia . IFN-γ . IL-4
Introduction Immune thrombocytopenia (ITP) is an autoimmune disease with heterogeneity, which is characterized by impaired platelet production and increased platelet destruction, resulting in a low platelet count (thrombocytopenia), which renders patients to have a bleeding risk [1, 2]. The development and
pathogenesis of ITP is much more complicated, involving several factors. Previous studies indicate that the main cause of ITP is the immunoglobulin G (IgG) autoantibodies against platelets, leading to formation of antigen-antibody complex, which will be phagocytosed and destroyed by macrophages in the reticuloendothelial system in the spleen through Fc receptor (FcR) engagement [3, 4].
Xiamin Wang, Jun Lu, and Guangyu Wei contributed equally to this study as first author * Lingyu Zeng [email protected] * Kailin Xu [email protected]
3
Key Laboratory of Bone Marrow Stem Cell, Xuzhou 221002, Jiangsu Province, China
4
Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China
5
Department of Hematology, The First People’s Hospital of Suqian City, Suqian 223899, China
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