Suppressive regulatory T cells(Treg cells)play a vital role in preventing autoimmunity and restraining excessive immune response to both self-and non-self-antigens.Studies on humans and mice show that the Forkhead box...Suppressive regulatory T cells(Treg cells)play a vital role in preventing autoimmunity and restraining excessive immune response to both self-and non-self-antigens.Studies on humans and mice show that the Forkhead box p3(Foxp3)is a key regulatory gene for the development and function of Treg cells.In zebrafish,Treg cells have been identified by using foxp3a as a reliable marker.However,little is known about the function of foxp3a and Treg cells in gonadal development and sex differentiation.Here,we show that foxp3a is essential for maintaining immune homeostasis in zebrafish testis development.We found that foxp3a was specifically expressed in a subset of T cells in zebrafish testis,while knockout of foxp3a led to deficiency of foxp3a-positive Treg cells in the testis.More than 80%of foxp3a^(-/-)mutants developed as subfertile males,and the rest of the mutants developed as fertile females with decreased ovulation.Further study revealed that foxp3a^(-/-)mutants had a delayed juvenile ovary-to-testis transition in definite males and sex reversal in about half of the definite females,which led to a dominance of later male development.Owing to the absence of foxp3a-positive Treg cells in the differentiating testis of foxp3a^(-/-)mutants,abundant T cells and macrophages expand to disrupt an immunosuppressive milieu,resulting in defective development of germ cells and gonadal somatic cells and leading to development of infertile males.Therefore,our study reveals that foxp3a-positive Treg cells play an essential role in the orchestration of gonadal development and sex differentiation in zebrafish.展开更多
2024年1月2日,上海交通大学医学院上海市免疫学研究所李斌课题组及合作团队在国际期刊Nature Communications在线发表了题为FOXP3+regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for ...2024年1月2日,上海交通大学医学院上海市免疫学研究所李斌课题组及合作团队在国际期刊Nature Communications在线发表了题为FOXP3+regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity的研究论文。该研究发现了肿瘤组织浸润Treg细胞中存在IFNγ依赖性的STAT1-IFITM3负反馈环路扰动,此环路通过平衡STAT1与IFITM3的动态表达,维持肿瘤浸润Treg细胞的功能稳定性。扰动此负反馈环路导致其失去平衡状态.展开更多
基金supported by the National Key Research and Development Program of China(2018YFD0900505 to Y.-A.Z.and 2018YFA0801000 to Y.S.)the National Natural Science Foundation of China(32025037 and 31721005 to Y.S.)。
文摘Suppressive regulatory T cells(Treg cells)play a vital role in preventing autoimmunity and restraining excessive immune response to both self-and non-self-antigens.Studies on humans and mice show that the Forkhead box p3(Foxp3)is a key regulatory gene for the development and function of Treg cells.In zebrafish,Treg cells have been identified by using foxp3a as a reliable marker.However,little is known about the function of foxp3a and Treg cells in gonadal development and sex differentiation.Here,we show that foxp3a is essential for maintaining immune homeostasis in zebrafish testis development.We found that foxp3a was specifically expressed in a subset of T cells in zebrafish testis,while knockout of foxp3a led to deficiency of foxp3a-positive Treg cells in the testis.More than 80%of foxp3a^(-/-)mutants developed as subfertile males,and the rest of the mutants developed as fertile females with decreased ovulation.Further study revealed that foxp3a^(-/-)mutants had a delayed juvenile ovary-to-testis transition in definite males and sex reversal in about half of the definite females,which led to a dominance of later male development.Owing to the absence of foxp3a-positive Treg cells in the differentiating testis of foxp3a^(-/-)mutants,abundant T cells and macrophages expand to disrupt an immunosuppressive milieu,resulting in defective development of germ cells and gonadal somatic cells and leading to development of infertile males.Therefore,our study reveals that foxp3a-positive Treg cells play an essential role in the orchestration of gonadal development and sex differentiation in zebrafish.
文摘2024年1月2日,上海交通大学医学院上海市免疫学研究所李斌课题组及合作团队在国际期刊Nature Communications在线发表了题为FOXP3+regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity的研究论文。该研究发现了肿瘤组织浸润Treg细胞中存在IFNγ依赖性的STAT1-IFITM3负反馈环路扰动,此环路通过平衡STAT1与IFITM3的动态表达,维持肿瘤浸润Treg细胞的功能稳定性。扰动此负反馈环路导致其失去平衡状态.
