Open AccessIndirubin modulates CD4 + T‐cell homeostasis via PD1/PTEN/AKT signalling pathway in immune thrombocytopenia
Author(s) -
Zhao Yajing,
Han Panpan,
Liu Lei,
Wang Xiaojie,
Xu Pengcheng,
Wang Haoyi,
Yu Tianshu,
Sun Yunqi,
Li Lizhen,
Sun Tao,
Liu Xinguang,
Zhou Hai,
Qiu Jihua,
Wang Liang,
Peng Jun,
Xu Shuqian,
Hou Ming
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14089
Subject(s) - indirubin , il 2 receptor , foxp3 , pi3k/akt/mtor pathway , effector , pten , protein kinase b , tensin , cancer research , immune system , biology , t cell , microbiology and biotechnology , immunology , signal transduction , art , visual arts , indigo
Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by an immune mediated decrease in platelet number. Disturbance of CD4 + T‐cell homeostasis with simultaneous decrease of CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) as well as unrestricted proliferation and activation of peripheral CD4 + effector T cells underpin the pathophysiology of ITP. Indirubin is an active ingredient of a traditional Chinese herb called Indigofera tinctoria L. which is clinically used for the treatment of ITP patients. Whether indirubin targets the Tregs/effector T cell‐axis to restore platelet number is unknown. In our in vitro studies, Indirubin could significantly enhance the number and function of Tregs and meanwhile dampen the activation of effector T cells in a dose‐dependent manner. Indirubin was observed to restore the expression of programmed cell‐death 1 (PD1) and phosphatase and tensin homolog (PTEN) on the CD4 + T cells of ITP patients, leading to the subsequent attenuation of the AKT/mTOR pathway. Furthermore, these observations were recapitulated in an active murine model of ITP with a prominent platelet response. Thus, our results identified a potentially novel mechanism of the therapeutic action of indirubin in the treatment of ITP through regulating the homeostasis of CD4 + T cells in a PD1/PTEN/AKT signalling pathway.