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,chemother...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:Den NTR)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.展开更多
Immunocytes,including the microglia,are crucial in the neurodegenerative process in old people.However,the understanding regarding microglia heterogeneity and other involved immunocytes remains elusive.We analyzed 26,...Immunocytes,including the microglia,are crucial in the neurodegenerative process in old people.However,the understanding regarding microglia heterogeneity and other involved immunocytes remains elusive.We analyzed 26,456 immunocytes from 12-and 26-month-old zebrafish brains at single-cell resolution.Microglia and T lymphocytes were detected in the brain at both time points.Two types of microglia were annotated,namely,ac+microglia and xr+microglia,which were clustered into subsets 1,2,3,4,5,and subsets 6,7,8,9,respectively.Diversified microglia predominated the adult brains and cooperated with T cells to perform the functions of immune response and neuronal nutrition.We validated the specific microglia markers.The novel transgenic lines,Tg(lgals3bpb:e GFP)and Tg(apoc1:e GFP),were created,which faithfully labeled ac+microglia and served as valuable labeling tools.However,the microglia population reduced while T cells of six subtypes intriguingly increased to serve as the primary immune cells in aged brains.Unlike in 12-month-old brains,T cells,together with microglia,exhibited a coordinated signature of inflammation in the 26-month-old brains.Our findings revealed the immunocytes atlas in aged zebrafish brains.It implied the involvement of microglia and T cells in the progression of neurodegeneration in aging.展开更多
基金supported by National Key Research and Development Project(2019YFA802703)National Natural Science Foundation of China Grants(331822033,31771623,32000568)+1 种基金Fundamental Research Funds for the Central Universities Grant(XDJK2020C041)Natural Science Foundation of Chongqing(CSTC2020JCYJMSXMX0104)。
文摘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:Den NTR)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.
基金supported by the National Key Research and Development Project (2019YFA802703)the National Natural Science Foundation of China (32270873,32000568,31822033)+1 种基金the Natural Science Foundation of Chongqing (CSTC2020JCYJ-MSXMX0104)Fundamental Research Funds for the Central Universities Grant (XDJK2020C041)。
文摘Immunocytes,including the microglia,are crucial in the neurodegenerative process in old people.However,the understanding regarding microglia heterogeneity and other involved immunocytes remains elusive.We analyzed 26,456 immunocytes from 12-and 26-month-old zebrafish brains at single-cell resolution.Microglia and T lymphocytes were detected in the brain at both time points.Two types of microglia were annotated,namely,ac+microglia and xr+microglia,which were clustered into subsets 1,2,3,4,5,and subsets 6,7,8,9,respectively.Diversified microglia predominated the adult brains and cooperated with T cells to perform the functions of immune response and neuronal nutrition.We validated the specific microglia markers.The novel transgenic lines,Tg(lgals3bpb:e GFP)and Tg(apoc1:e GFP),were created,which faithfully labeled ac+microglia and served as valuable labeling tools.However,the microglia population reduced while T cells of six subtypes intriguingly increased to serve as the primary immune cells in aged brains.Unlike in 12-month-old brains,T cells,together with microglia,exhibited a coordinated signature of inflammation in the 26-month-old brains.Our findings revealed the immunocytes atlas in aged zebrafish brains.It implied the involvement of microglia and T cells in the progression of neurodegeneration in aging.
