Autophagy and immunity share the property of being auto-protective for the organism.Autophagy is an important degradation pathway that buffers nutrient deprivation by recycling macromolecules in organisms from yeast t...Autophagy and immunity share the property of being auto-protective for the organism.Autophagy is an important degradation pathway that buffers nutrient deprivation by recycling macromolecules in organisms from yeast to man.Perturbations in autophagy are associated with inflammation and cancer development.Emerging studies have characterized the molecular details regarding how autophagy is controlled by immune cells.Among these,dendritic cells(DCs)are one of the most potent professional antigen-presenting cells critical for the activation of naïve T cells to maintain immune tolerance and drive protective immunity to infection and cancer.DCs undergo functional maturation that can either lead to an immunostimulatory phenotype,as in the context of infection,or to a tolerogenic phenotype associated with immunosuppression to self-antigens,as well as to cancer.An increasing number of recent studies has characterized the involvement of autophagy in DC functions in various physiological and pathological contexts.Here,we provide a comprehensive review of these outcomes and discuss the limitation of the models used and the forefront of the knowledge concerning the crosstalk between autophagy and DC biology.展开更多
Neutrophils are crucial for immunity and play important roles in inflammatory diseases;however,mouse models selectively deficient in neutrophils are limited,and neutrophil-specific diphtheria toxin(DT)-based depletion...Neutrophils are crucial for immunity and play important roles in inflammatory diseases;however,mouse models selectively deficient in neutrophils are limited,and neutrophil-specific diphtheria toxin(DT)-based depletion system has not yet been established.In this study,we generated a novel knock-in mouse model expressing diphtheria toxin receptor(DTR)under control of the endogenous Ly6G promoter.We showed that DTR expression was restricted to Ly6G+neutrophils and complete depletion of neutrophils could be achieved by DT treatment at 24-48 h intervals.We characterized the effects of specific neutrophil depletion in mice at steady-state,with acute inflammation and during tumor growth.Our study presents a valuable new tool to study the roles of neutrophils in the immune system and during tumor progression.展开更多
基金The present work was supported by funding from the Horizon 2020 work program of the Marie Curie Actions grant agreement number 57212 MCNTMTDC(GG)La Ligue Contre le Cancer fellowship(GG)Equipe Labellisee LNCC grant(TL).
文摘Autophagy and immunity share the property of being auto-protective for the organism.Autophagy is an important degradation pathway that buffers nutrient deprivation by recycling macromolecules in organisms from yeast to man.Perturbations in autophagy are associated with inflammation and cancer development.Emerging studies have characterized the molecular details regarding how autophagy is controlled by immune cells.Among these,dendritic cells(DCs)are one of the most potent professional antigen-presenting cells critical for the activation of naïve T cells to maintain immune tolerance and drive protective immunity to infection and cancer.DCs undergo functional maturation that can either lead to an immunostimulatory phenotype,as in the context of infection,or to a tolerogenic phenotype associated with immunosuppression to self-antigens,as well as to cancer.An increasing number of recent studies has characterized the involvement of autophagy in DC functions in various physiological and pathological contexts.Here,we provide a comprehensive review of these outcomes and discuss the limitation of the models used and the forefront of the knowledge concerning the crosstalk between autophagy and DC biology.
基金funded by the National Natural Science Foundation of China(81471595 to YL,81601360 to LZ,U1904157 to LL)The animal model development was supported by 111 Program(D20036).
文摘Neutrophils are crucial for immunity and play important roles in inflammatory diseases;however,mouse models selectively deficient in neutrophils are limited,and neutrophil-specific diphtheria toxin(DT)-based depletion system has not yet been established.In this study,we generated a novel knock-in mouse model expressing diphtheria toxin receptor(DTR)under control of the endogenous Ly6G promoter.We showed that DTR expression was restricted to Ly6G+neutrophils and complete depletion of neutrophils could be achieved by DT treatment at 24-48 h intervals.We characterized the effects of specific neutrophil depletion in mice at steady-state,with acute inflammation and during tumor growth.Our study presents a valuable new tool to study the roles of neutrophils in the immune system and during tumor progression.
