生物
T细胞
造血
淋巴细胞生成
CXCR4型
细胞生物学
癌症研究
骨髓
严重联合免疫缺陷
T细胞白血病
干细胞
免疫学
免疫系统
淋巴瘤
生物化学
基因
趋化因子
作者
Yi‐Jie Huang,Yueping Huang,Jin‐Qiu Xia,Zhou-Ping Fu,Yifan Chen,Yi-Peng Huang,Aiyuan Ma,Wen‐Tao Hou,Chen Yuxing,Xiaoquan Qi,Liping Gao,Cheng‐Bin Xiang
标识
DOI:10.1016/j.jgg.2022.04.007
摘要
T cells play a critical role in immunity to protect against pathogens and malignant cells. T cell immunodeficiency is detrimental, especially when T cell perturbation occurs during severe infection, irradiation, chemotherapy, and age-related thymic atrophy. Therefore, strategies that enhance T cell reconstitution provide considerable benefit and warrant intensive investigation. Here, we report the construction of a T cell ablation model in Tg(coro1a:DenNTR) zebrafish via metronidazole administration. The nascent T cells are mainly derived from the hematopoietic cells migrated from the kidney, the functional homolog of bone marrow and the complete recovery time is 6.5 days post-treatment. The cxcr4b gene is upregulated in the responsive hematopoietic cells. Functional interference of CXCR4 via both genetic and chemical manipulations does not greatly affect T lymphopoiesis, but delays T cell regeneration by disrupting hematopoietic migration. In contrast, cxcr4b accelerates the replenishment of hematopoietic cells in the thymus. Consistently, Cxcl12b, a ligand of Cxcr4, is increased in the thymic epithelial cells of the injured animals. Decreased or increased expression of Cxcl12b results in compromised or accelerated T cell recovery, respectively, similar to those observed with Cxcr4b. Taken together, our study reveals a role of CXCR4-CXCL12 signaling in promoting T cell recovery and provides a promising target for the treatment of immunodeficiency due to T cell injury.
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