Group 3 innate lymphoid cells(ILC3s)play important roles in maintaining intestinal homeostasis by protecting the host from pathogen infections and tissue inflammation.The transcription factor PLZF(promyelocytic leukem...Group 3 innate lymphoid cells(ILC3s)play important roles in maintaining intestinal homeostasis by protecting the host from pathogen infections and tissue inflammation.The transcription factor PLZF(promyelocytic leukemia zinc finger),encoded by zinc finger BTB domain containing 16(Zbtb16),is highly and transiently expressed in ILC precursors(ILCPs).However,the role of PLZF in regulating ILC3 development and function remains unknown.Here,we show that PLZF was specifically expressed in mature intestinal ILC3s compared with other ILC subsets.PLZF was dispensable for ILC3 development.However,PLZF deficiency in ILC3s resulted in increased innate interleukin-22(IL-22)secretion and protection against gut infection and inflammation.Mechanistically,PLZF negatively regulated IL-22 expression by ILC3s in a cell-intrinsic manner by binding to the IL-22 promoter region for transcriptional repression.Together,our data suggest that PLZF restricts intestinal ILC3 function to regulate gut immune homeostasis.展开更多
O-Mannosylation plays a vital role in the regulation of a variety range of biological processes,for instance,brain and muscle development.However,the precise function remains largely unknown due to its innate heteroge...O-Mannosylation plays a vital role in the regulation of a variety range of biological processes,for instance,brain and muscle development.However,the precise function remains largely unknown due to its innate heterogeneity.In this regard,it is still welcome to develop efficient methods to access diverse structurally-defined glycopeptides.In this study,a diversity-oriented assembly of O-mannosylα-dystroglycan(α-DG)glycopeptides has been achieved via a chemoenzymatic strategy.This strategy features(i)gram scale divergent synthesis of core m1,core m2 and core m3 mannosylated amino acids from judiciously designed protecting group strategies and chemical glycosidation;(i)efficient glycopeptide assembly via the optimized microwave-assisted solid phase peptide synthesis(SPpS);and(ii)enzymatic elaboration of the core glycan structures to install galactosyl and sialyl-galactosyl moieties.The efficiency and flexibility of this chemoenzymatic approach was demonstrated with the construction of 12 glycopeptides with different core m1,core m2 and core m3 mannosyl glycans,including a core m2 glycopeptide bearing a heptasaccharide for the first time.展开更多
基金grant 2020YFA0509200(to LS)from the Ministry of Science and Technology of Chinagrant 81971487(to LS)from the National Natural Science Foundation of China+1 种基金grants 20ZR1430200 and 20142202300(to LS)from the Science and Technology Commission of Shanghai Municipalitygrant 20194Y0275(to JS)from the Shanghai Municipal Health Commission,and the Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases.
文摘Group 3 innate lymphoid cells(ILC3s)play important roles in maintaining intestinal homeostasis by protecting the host from pathogen infections and tissue inflammation.The transcription factor PLZF(promyelocytic leukemia zinc finger),encoded by zinc finger BTB domain containing 16(Zbtb16),is highly and transiently expressed in ILC precursors(ILCPs).However,the role of PLZF in regulating ILC3 development and function remains unknown.Here,we show that PLZF was specifically expressed in mature intestinal ILC3s compared with other ILC subsets.PLZF was dispensable for ILC3 development.However,PLZF deficiency in ILC3s resulted in increased innate interleukin-22(IL-22)secretion and protection against gut infection and inflammation.Mechanistically,PLZF negatively regulated IL-22 expression by ILC3s in a cell-intrinsic manner by binding to the IL-22 promoter region for transcriptional repression.Together,our data suggest that PLZF restricts intestinal ILC3 function to regulate gut immune homeostasis.
基金This work is financially supported by the National Natural Science Foundation of China(Grant Nos.22177061,92053110,21977063,21907056)the China Postdoctoral Science Foundation(2020M680090)+2 种基金the Shenzhen Science and Technology Program(RCBS20200714114957255)the Open Projects Fund of Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology(2021CCG01&02)the Central Government Guide Local Science and Technology Development Funds(YDZX20203700002579).
文摘O-Mannosylation plays a vital role in the regulation of a variety range of biological processes,for instance,brain and muscle development.However,the precise function remains largely unknown due to its innate heterogeneity.In this regard,it is still welcome to develop efficient methods to access diverse structurally-defined glycopeptides.In this study,a diversity-oriented assembly of O-mannosylα-dystroglycan(α-DG)glycopeptides has been achieved via a chemoenzymatic strategy.This strategy features(i)gram scale divergent synthesis of core m1,core m2 and core m3 mannosylated amino acids from judiciously designed protecting group strategies and chemical glycosidation;(i)efficient glycopeptide assembly via the optimized microwave-assisted solid phase peptide synthesis(SPpS);and(ii)enzymatic elaboration of the core glycan structures to install galactosyl and sialyl-galactosyl moieties.The efficiency and flexibility of this chemoenzymatic approach was demonstrated with the construction of 12 glycopeptides with different core m1,core m2 and core m3 mannosyl glycans,including a core m2 glycopeptide bearing a heptasaccharide for the first time.
