2. Academic Validation
  3. Targeting interleukin-2-inducible T cell kinase ameliorates immune-mediated aplastic anemia

Targeting interleukin-2-inducible T cell kinase ameliorates immune-mediated aplastic anemia

  • Cancer Immunol Immunother. 2025 Apr 29;74(6):188. doi: 10.1007/s00262-025-04040-0.
Weiwang Li # 1 2 3,  Yu Lian # 4,  Lele Zhang 1 2 3,  Ruonan Li 1 2 3,  Qian Liang 5,  Jin Mao 1 2 3,  Chen Qiu 1 2,  Haoyuan Li 1 2,  Ke Huang 1 2 3,  Qiaoli Li 1 2 3,  Yucan Shen 1 2 3,  Fei Yang 1 2 3,  Linzhu Tian 1 2 3,  Tingfang Xiao 1 2 3,  Shilong Gu 1 2 3,  Hong Pan 1 2 3,  Zhen Gao 1 2 3,  Jingyu Zhao 1 2 3,  Liwei Fang 1 2 3,  Meili Ge 1 2 3,  Weiping Yuan 6 7,  Yajing Chu 8 9,  Jun Shi 10 11 12
Affiliations

Affiliations

  • 1 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China.
  • 2 Tianjin Institutes of Health Science, Tianjin, 301600, China.
  • 3 Red Blood Cell Diseases Center and Regenerative Medicine Clinic, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, China.
  • 4 Department of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.
  • 5 Zhoukou Center Hospital, Zhoukou, 466099, China.
  • 6 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China. wpyuan@ihcams.ac.cn.
  • 7 Tianjin Institutes of Health Science, Tianjin, 301600, China. wpyuan@ihcams.ac.cn.
  • 8 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China. chuyajing@ihcams.ac.cn.
  • 9 Tianjin Institutes of Health Science, Tianjin, 301600, China. chuyajing@ihcams.ac.cn.
  • 10 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China. shijun@ihcams.ac.cn.
  • 11 Tianjin Institutes of Health Science, Tianjin, 301600, China. shijun@ihcams.ac.cn.
  • 12 Red Blood Cell Diseases Center and Regenerative Medicine Clinic, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, China. shijun@ihcams.ac.cn.
  • # Contributed equally.
PMID: 40299061 DOI: 10.1007/s00262-025-04040-0
Abstract

Allogeneic stem cell transplant and immunosuppressive therapy (IST) are the current standard treatments for patients with aplastic anemia (AA). However, IST also carries significant risks and side effects, and up to 30-50% of patients experienced refractory or relapsed disease following IST. Treating AA remains challenging and novel efficient therapies are in critical need. The IL-2 inducible T-cell kinase (Itk) plays a crucial role in the T cell response and functions as a regulator of T cell activity. While Itk inhibition has shown promise in various immune-related disorders, its potential role in the pathophysiology of AA has not been thoroughly investigated. We observed elevated level of phosphorylated Itk in T cells from AA patients and AA mouse models. Moreover, we found that both treatment with an Itk inhibitor or conditional depletion of Itk in donor mice alleviated bone marrow hypoplasia, improved cytopenia, and extended survival rates. Notably, Itk inhibition orchestrates T cell quantity and function by reducing T cell infiltration and suppressing the secretion of key inflammatory cytokines in AA mice. Our data suggest that Itk inhibitor could potentially offer a new therapeutic strategy for AA.

Keywords

Aplastic anemia; IL-2-induced T cell kinase; T lymphocytes; Targeted therapy.

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