Tacrolimus ameliorates thrombocytopenia in an ITP mouse model

Ann Hematol. 2020 Oct;99(10):2315-2322. doi: 10.1007/s00277-020-04203-2. Epub 2020 Jul 29.

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by lower platelet count resulting from immune cells-mediated 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: IFN-γ; IL-4; Immune thrombocytopenia; Tacrolimus.

MeSH terms

  • Animals
  • Blood Platelets / immunology
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Isoantibodies / blood
  • Mice
  • Mice, Inbred C57BL
  • Purpura, Thrombocytopenic, Idiopathic / drug therapy*
  • Purpura, Thrombocytopenic, Idiopathic / genetics
  • Purpura, Thrombocytopenic, Idiopathic / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Specific Pathogen-Free Organisms
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • Tacrolimus / therapeutic use*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics

Substances

  • Cytokines
  • Immunosuppressive Agents
  • Isoantibodies
  • RNA, Messenger
  • Transcription Factors
  • Tacrolimus