Investigations into the nitrogen-fixing symbiosis between legumes and rhizobia can yield innovative strategies for sustainable agriculture.Legume species of the Inverted Repeat-Lacking Clade(IRLC)and the Dalbergioids,...Investigations into the nitrogen-fixing symbiosis between legumes and rhizobia can yield innovative strategies for sustainable agriculture.Legume species of the Inverted Repeat-Lacking Clade(IRLC)and the Dalbergioids,can utilize nodule cysteine-rich(NCR)peptides,a diverse family of peptides characterized by four or six highly conserved cysteine residues,to communicate with their microbial symbionts.These peptides,many of which exhibit antimicrobial properties,induce profound differentiation of bacteroids(semi-autonomous forms of bacteria)within nodule cells.This terminal differentiation endows the bacteroids with the ability to fix nitrogen,at the expense of their reproductive capacity.Notably,a significant number of NCR peptides is expressed in the nodule fixation zone,where the bacteroids have already reached terminal differentiation.Recent discoveries,through forward genetics approaches,have revealed that the functions of NCR peptides extend beyond antimicrobial effects and the promotion of differentiation.They also play a critical role in sustaining the viability of terminally differentiated bacteroids within nodule cells.These findings underscore the multifaceted functions of NCR peptides and highlight the importance of these peptides in mediating communications between host cells and the terminally differentiated bacteroids.展开更多
As chronic antigenic stimulation from infection and autoimmunity is a feature of primary antibody deficiency(PAD),analysis of affected patients could yield insights into T-cell differentiation and explain how environm...As chronic antigenic stimulation from infection and autoimmunity is a feature of primary antibody deficiency(PAD),analysis of affected patients could yield insights into T-cell differentiation and explain how environmental exposures modify clinical phenotypes conferred by single-gene defects.CD57 marks dysfunctional T cells that have differentiated after antigenic stimulation.Indeed,while circulating CD57^(+)CD4^(+)T cells are normally rare,we found that they are increased in patients with PAD and markedly increased with CTLA4 haploinsufficiency or blockade.We performed single-cell RNA-seq analysis of matched CD57^(+)CD4^(+)T cells from blood and tonsil samples.Circulating CD57^(+)CD4^(+)T cells(CD4cyt)exhibited a cytotoxic transcriptome similar to that of CD8^(+)effector cells,could kill B cells,and inhibited B-cell responses.CTLA4 restrained the formation of CD4cyt.While CD57 also marked an abundant subset of follicular helper T cells,which is consistent with their antigen-driven differentiation,this subset had a preexhaustion transcriptomic signature marked by TCF7,TOX,and ID3 expression and constitutive expression of CTLA4 and did not become cytotoxic even after CTLA4 inhibition.Thus,CD57^(+)CD4^(+)T-cell cytotoxicity and exhaustion phenotypes are compartmentalised between blood and germinal centers.CTLA4 is a key modifier of CD4^(+)T-cell cytotoxicity,and the pathological CD4cyt phenotype is accentuated by infection.展开更多
基金funded by the National Natural Science Foundation of China (Grant Nos.32441035, 32470255, 32070271, and 32161133006 to H.P.,32200201 to F.G.)Distinguished Young Scholar Grant of Hunan Province, 2024JJ2014, to H.P.Young Scholar Grant of Natural Science Foundation of Hunan Province,2024JJ6132, to Y.J.
文摘Investigations into the nitrogen-fixing symbiosis between legumes and rhizobia can yield innovative strategies for sustainable agriculture.Legume species of the Inverted Repeat-Lacking Clade(IRLC)and the Dalbergioids,can utilize nodule cysteine-rich(NCR)peptides,a diverse family of peptides characterized by four or six highly conserved cysteine residues,to communicate with their microbial symbionts.These peptides,many of which exhibit antimicrobial properties,induce profound differentiation of bacteroids(semi-autonomous forms of bacteria)within nodule cells.This terminal differentiation endows the bacteroids with the ability to fix nitrogen,at the expense of their reproductive capacity.Notably,a significant number of NCR peptides is expressed in the nodule fixation zone,where the bacteroids have already reached terminal differentiation.Recent discoveries,through forward genetics approaches,have revealed that the functions of NCR peptides extend beyond antimicrobial effects and the promotion of differentiation.They also play a critical role in sustaining the viability of terminally differentiated bacteroids within nodule cells.These findings underscore the multifaceted functions of NCR peptides and highlight the importance of these peptides in mediating communications between host cells and the terminally differentiated bacteroids.
基金NHMRC grants APP1113577(MCC,CGV)and APP1079648(MCC,CGV)grant APP1130330 awarded through the Priority-drive Collaborative Cancer Research Scheme and funded by Cancer Australia(MCC,DY,SY).
文摘As chronic antigenic stimulation from infection and autoimmunity is a feature of primary antibody deficiency(PAD),analysis of affected patients could yield insights into T-cell differentiation and explain how environmental exposures modify clinical phenotypes conferred by single-gene defects.CD57 marks dysfunctional T cells that have differentiated after antigenic stimulation.Indeed,while circulating CD57^(+)CD4^(+)T cells are normally rare,we found that they are increased in patients with PAD and markedly increased with CTLA4 haploinsufficiency or blockade.We performed single-cell RNA-seq analysis of matched CD57^(+)CD4^(+)T cells from blood and tonsil samples.Circulating CD57^(+)CD4^(+)T cells(CD4cyt)exhibited a cytotoxic transcriptome similar to that of CD8^(+)effector cells,could kill B cells,and inhibited B-cell responses.CTLA4 restrained the formation of CD4cyt.While CD57 also marked an abundant subset of follicular helper T cells,which is consistent with their antigen-driven differentiation,this subset had a preexhaustion transcriptomic signature marked by TCF7,TOX,and ID3 expression and constitutive expression of CTLA4 and did not become cytotoxic even after CTLA4 inhibition.Thus,CD57^(+)CD4^(+)T-cell cytotoxicity and exhaustion phenotypes are compartmentalised between blood and germinal centers.CTLA4 is a key modifier of CD4^(+)T-cell cytotoxicity,and the pathological CD4cyt phenotype is accentuated by infection.
