Thymic-derived tolerizing dendritic cells are upregulated in the spleen upon treatment with intravenous immunoglobulin in a murine model of immune thrombocytopenia

Platelets. 2017 Jul;28(5):521-524. doi: 10.1080/09537104.2016.1246718. Epub 2016 Nov 25.

Abstract

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by low platelet counts. First-line treatment includes intravenous immunoglobulin (IVIg), however, its working mechanism remains incompletely understood. We investigated splenic and thymic dendritic cell (DC) subsets upon IVIg treatment in a well-characterized active murine model of ITP. During active disease, there was a significant peripheral deficiency of splenic tolerizing SIRPα+ DCs which could be rescued by IVIg therapy, increasing platelet counts. These splenic tolerizing DC changes were associated with an abrogation of the thymic-retention of tolerizing DCs, suggesting that IVIg may raise platelet counts in ITP by modulating peripheral numbers of tolerizing DCs.

Keywords: Dendritic cells; IVIg; immune thrombocytopenia.

MeSH terms

  • Animals
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Disease Models, Animal
  • Immune Tolerance / drug effects*
  • Immunoglobulins, Intravenous / pharmacology*
  • Mice
  • Mice, Knockout
  • Mice, SCID
  • Purpura, Thrombocytopenic, Idiopathic* / drug therapy
  • Purpura, Thrombocytopenic, Idiopathic* / immunology
  • Purpura, Thrombocytopenic, Idiopathic* / pathology
  • Spleen / immunology*
  • Spleen / pathology
  • Thymus Gland / immunology*
  • Thymus Gland / pathology
  • Up-Regulation / drug effects*
  • Up-Regulation / immunology

Substances

  • Immunoglobulins, Intravenous