Li Weiwang, Lian Yu, Zhang Lele, Li Ruonan, Liang Qian, Mao Jin, Qiu Chen, Li Haoyuan, Huang Ke, Li Qiaoli, Shen Yucan, Yang Fei, Tian Linzhu, Xiao Tingfang, Gu Shilong, Pan Hong, Gao Zhen, Zhao Jingyu, Fang Liwei, Ge Meili, Yuan Weiping, Chu Yajing, Shi Jun
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.
Tianjin Institutes of Health Science, Tianjin, 301600, China.
Cancer Immunol Immunother. 2025 Apr 29;74(6):188. doi: 10.1007/s00262-025-04040-0.
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.
异基因干细胞移植和免疫抑制治疗（IST）是目前再生障碍性贫血（AA）患者的标准治疗方法。然而，IST也存在重大风险和副作用，高达30%-50%的患者在接受IST后出现难治性或复发性疾病。治疗AA仍然具有挑战性，急需新型高效的治疗方法。白细胞介素-2诱导型T细胞激酶（ITK）在T细胞反应中起关键作用，是T细胞活性的调节剂。虽然ITK抑制在各种免疫相关疾病中已显示出前景，但其在AA病理生理学中的潜在作用尚未得到充分研究。我们观察到AA患者和AA小鼠模型的T细胞中磷酸化ITK水平升高。此外，我们发现用ITK抑制剂治疗或在供体小鼠中条件性敲除Itk均可减轻骨髓发育不全，改善血细胞减少，并延长生存率。值得注意的是，ITK抑制通过减少T细胞浸润和抑制AA小鼠关键炎性细胞因子的分泌来协调T细胞数量和功能。我们的数据表明，ITK抑制剂可能为AA提供一种新的治疗策略。
