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

• PMID: 31877304
• DOI: 10.1016/j.yexcr.2019.111801

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.