CXCR4-CXCL12 axis promotes the efficient T cell reconstitution by the HSPCs immigration

ABSTRACT: T cells are essentially involved in safeguarding homeostasis through fighting against the pathogens and malignant cells. T cell immunodeficiency, especially their perturbation in the severe infection, irradiation, chemotherapy, and thymic atrophy in ageing, is detrimental. Therefore, strategies that enhance T cell reconstitution provide considerable benefit and warrant intensive investigation. Here, we constructed a T cells ablation model in Tg(coro1a:DenNTR) zebrafish via administrating a proper volume of metronidazole (MTZ). T cells completely recovered at 6.5 days post treatment (dpt). The nascent regenerated T cells were mainly derived from the immigration of hematopoietic stem/progenitor cells (HSPCs) in the kidney, the functional homologue of BM. cxcr4b, but not ccr9 nor ccr7, was drastically unregulated in the responsive HSPCs. Functional interference of CXCR4 via both genetic and chemical assays yielded limited influence in T lymphopoiesis but notably delayed T cells regeneration by a destroyed HSPCs migration. In contrast, hematopoietic providing cxcr4b in Tg:(coro1a:cxcr4b) accelerates thymus-replenishment of HSPCs. Correspondingly, Cxcl12b, the ligand of Cxcr4, exhibited impressive increment presentation in the thymic epithelial cells of injured animals. Interfering or overacting Cxcl12b in either cxcl12b-/- mutants or Tg(hsp70:cxcl12b) recapitulated the similarly compromised or promoted T cells recovery as that seen in Cxcr4b scenario. Therefore, CXCR4-CXCL12 axis plays a crucial role in promoting thymocyte reconstitution but did not influence T cell development. Our study discloses a special role of CXCR4-CXCL12 signaling in promoting T cells recovery and provides a promising target to mitigate T cell immunodeficiency.

ORGANISM(S): Danio rerio

PROVIDER: GSE190921 | GEO | 2022/08/29

REPOSITORIES: GEO