Targeting interleukin-2-inducible T cell kinase ameliorates immune-mediated aplastic anemia
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.
Authors
- Yajing Chu (ORCID: https://orcid.org/0000-0001-6239-1519)
- Ting Xiao (ORCID: https://orcid.org/0000-0002-9000-1909)
- Qian Liang (ORCID: https://orcid.org/0000-0003-3985-2633)
- Lele Zhang
- Jun Shi (ORCID: https://orcid.org/0000-0002-8531-0483)
- Liwei Fang (ORCID: https://orcid.org/0009-0009-3605-3562)
- Zhen Gao (ORCID: https://orcid.org/0000-0001-7427-6032)
- Jingyu Zhao
- Fei Yang (ORCID: https://orcid.org/0000-0002-2768-5949)
- Ya Shen (ORCID: https://orcid.org/0000-0002-0792-4279)
- Meili Ge (ORCID: https://orcid.org/0000-0002-8229-4203)
- Weiwang Li
- Weiping Yuan
- Haoyuan Li (ORCID: https://orcid.org/0000-0002-2554-4835)
- Ke Huang (ORCID: https://orcid.org/0000-0003-1854-7840)
- Ruonan Li (ORCID: https://orcid.org/0000-0002-9581-2620)
- Chen Qiu (ORCID: https://orcid.org/0009-0006-9323-3867)
- Lin Tian (ORCID: https://orcid.org/0000-0003-3661-4453)
- Yu Lian (ORCID: https://orcid.org/0000-0003-3688-5499)
- Hong Pan (ORCID: https://orcid.org/0000-0002-0458-2613)
- Qiaoli Li (ORCID: https://orcid.org/0000-0002-1741-6542)
- Jin Mao (ORCID: https://orcid.org/0000-0002-0629-448X)
- Shenyan Gu
Institutions
- Shanxi Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Institute of Hematology & Blood Diseases Hospital (CN)
- Shanxi Academy of Medical Sciences (CN)
Publication Details
- Journal
- Cancer Immunology Immunotherapy
- Published
- 2025-04-29
- DOI
- https://doi.org/10.1007/s00262-025-04040-0
- Primary Topic
- Hematopoietic Stem Cell Transplantation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Chinese Academy of Medical Sciences
- National Key Research and Development Program of China