Exp Cell Res.2020 Mar 1;388(1):111801.doi: 10.1016/j.yexcr.2019.111801.Epub 2019 Dec 23.

Interleukin 9 prevents immune thrombocytopenia in mice via JAK/STAT5 signaling

Yaling Zheng  1 Yanjie He  2 Min Xiao  3 Wuju Zhang  3 Wei Xia  3 Hongling Hu  3 Lingling Mao  3 Anling Liu  3 Zhenguo Chen  3 Xiaochun Bai  4 Yuhua Li  5 Affiliations

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by autoimmune-mediated platelet destruction and impaired platelet production, which can lead to an increased risk of bleeding. The clinical management of ITP currently remains a challenge for hematologists. We explored the role of interleukin-9 (IL-9) in the treatment of CD41-induced ITP, and investigated its underlying mechanisms in a CD41-induced ITP mouse model. IL-9 treatment increased the numbers of mature megakaryocytes (CD41+CD42d+) and CD41+Sca-1+ cells in the bone marrow in these model mice, while IL-9 receptor (IL-9R) small interfering RNA (siRNA) inhibited the process. Moreover, phosphorylated signal transducer and activator of transcription 5 (STAT5), as a downstream molecule of IL-9R, was increased after IL-9 treatment. We next investigated the source of IL-9 in bone marrow, osteoblasts produced the highest level of IL-9. These results confirmed that IL-9 could prevent CD41-induced ITP in BALB/c mice by regulating osteoblasts and activating IL-9R/STAT5 signaling in megakaryocytes, thus providing further evidence for IL-9 as a promising therapeutic agent for the treatment of ITP.

Keywords: Immune thrombocytopenia; Interleukin 9; STAT5.

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