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Volume 49 Issue 12
Dec.  2022
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Article Navigation >  Journal of Genetics and Genomics  > 2022  >  49(12): 1138-1150

The CXCR4-CXCL12 axis promotes T cell reconstitution via efficient hematopoietic immigration

doi: 10.1016/j.jgg.2022.04.005
  •  

    a. Institute of Developmental Biology and Regenerative Medicine, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Southwest University, Chongqing 400715, China;

  •  

    b. Research Center of Stem Cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, China

Funds:

This work was supported by National Key Research and Development Project (2019YFA802703)

National Natural Science Foundation of China Grants (331822033, 31771623

Fundamental Research Funds for the Central Universities Grant (XDJK2020C041), and Natural Science Foundation of Chongqing (CSTC2020JCYJ-MSXMX0104).

32000568)

  • Received Date: 2021-12-18
  • Accepted Date: 2022-04-13
  • Rev Recd Date: 2022-04-07
  • Publish Date: 2022-04-26
    Abstract
  • 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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