Abstract
Indirubin, a traditional Chinese medicine, is used to treat autoimmune diseases in clinics. However, the effects of indirubin on the immunosuppressive CD4+CD25+Foxp3+ regulatory T cells (Treg) have not been addressed. Thus, we aimed to investigate the effects of indirubin on CD4+CD25+Treg cells in immune thrombocytopenia (ITP) CBA mice, which were established by immunization with Wistar rat platelets. 50 mg/kg indirubin treatment daily for 4 weeks significantly decreased anti-platelet antibody production and prevented the decrease of platelets caused by immunization in ITP mice. Consistently, indirubin significantly enhanced the percentage and cell number of CD4+CD25+Foxp3+Treg cells in the peripheral blood, spleen and lymph nodes. We also observed a significant increase of the frequency and cell number of CD4+CD25+Foxp3+Treg cells in the thymus upon indirubin treatment. Furthermore, CD4+CD25+Treg cells from indirubin-treated mice showed similar immunosuppression on T effector cells as compared to those from control mice. Altogether, indirubin ameliorates ITP by enhancing CD4+CD25+Foxp3+Treg cell level with preserving immunosuppressive function.
Highlights
Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder characterized by persistent thrombocytopenia in children, caused by the production of anti-platelet autoantibody against platelet membrane glycoproteins which mediates the destruction of platelets in the reticuloendothelial system, especially in the spleen [1]
It has been reported that decreased number and/or function of CD4+CD25+ forkhead box protein 3 (Foxp3)+ regulatory T (Treg) cells, which are crucial for self-tolerance, represent one possible mechanism leading to the development of ITP [2,3]
Indirubin ameliorates transient thrombocytopenia in mice immunized with Wistar platelets To investigate whether indirubin treatment could prevent the occurrence of ITP caused by immunization with rat platelets in CBA mice, which is a well-established ITP mouse model [14]
Summary
Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder characterized by persistent thrombocytopenia in children, caused by the production of anti-platelet autoantibody against platelet membrane glycoproteins which mediates the destruction of platelets in the reticuloendothelial system, especially in the spleen [1]. It has been reported that decreased number and/or function of CD4+CD25+ Foxp3+ regulatory T (Treg) cells, which are crucial for self-tolerance, represent one possible mechanism leading to the development of ITP [2,3]. Indirubin is a traditional Chinese medicine currently used for the treatment of chronic myelocytic leukemia [4] and certain autoimmune conditions and anti-inflammatory therapy [5,6]. The effects of indirubin on the immunosuppressive CD4+CD25+ Treg cells have not PLOS ONE | DOI:10.1371/journal.pone.0142634. The effects of indirubin on the immunosuppressive CD4+CD25+ Treg cells have not PLOS ONE | DOI:10.1371/journal.pone.0142634 November 16, 2015
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call