PUBLICATION
The CXCR4-CXCL12 axis promotes T-cell reconstitution via efficient hematopoietic immigration
- Authors
- Zhao, F., Lu, Y., Li, Z., He, J., Cui, N., Luo, L., Li, L.
- ID
- ZDB-PUB-220429-19
- Date
- 2022
- Source
- Journal of genetics and genomics = Yi chuan xue bao 49(12): 1138-1150 (Journal)
- Registered Authors
- Li, Li, Luo, Lingfei
- Keywords
- Cxcl12b, Cxcr4b, Immigration, T-cell reconstitution, Zebrafish
- Datasets
- GEO:GSE190921
- MeSH Terms
-
- Animals
- Cell Movement
- Signal Transduction
- T-Lymphocytes*
- Zebrafish*/genetics
- Zebrafish Proteins/genetics
- PubMed
- 35483564 Full text @ J. Genet. Genomics
Citation
Zhao, F., Lu, Y., Li, Z., He, J., Cui, N., Luo, L., Li, L. (2022) The CXCR4-CXCL12 axis promotes T-cell reconstitution via efficient hematopoietic immigration. Journal of genetics and genomics = Yi chuan xue bao. 49(12):1138-1150.
Abstract
T cells play critical roles 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping