The programmed cell death-1(PD-1)/PD-ligand 1(PD-L1)pathway is critical for normal pregnancy by promoting regulatory T(Treg)cell development and inhibiting the Th17 response.However,the relationship between the PD-1/P...The programmed cell death-1(PD-1)/PD-ligand 1(PD-L1)pathway is critical for normal pregnancy by promoting regulatory T(Treg)cell development and inhibiting the Th17 response.However,the relationship between the PD-1/PD-L1 pathway and the Treg/Th17 imbalance in pre-eclampsia(PE)is an enigma.In this study,decreased PD-1 and PD-L1 expression and a Treg/Th17 imbalance were observed at the maternal-fetal interface in PE.The regulatory effects of the PD-1/PD-L1 pathway on the Treg and Th17 cell quantities were determined in vitro by targeting T-cell proliferation,differentiation and transdifferentiation.First,decreased PD-1 expression might contribute to a higher Th17 cell frequency by promoting proliferation in PE.Second,the percentages of Treg but not Th17 cells differentiated from peripheral naive CD4+T cells were increased by PD-L1 Fc administration.This effect was accompanied by decreased PI3K/AKT/m-TOR and increased PTEN mRNA expression and was completely reversed by PD-1 blockade.Finally,the percentage of IL-17-producing Treg cells increased and was positively associated with the Th17 cell frequency in PE.Increased RORγt and IL-17 but not Foxp3 and IL-10 mRNA expression by Treg cells was observed with PD-1 blockade.Similar findings occurred when Treg cells were exposed to IL-6/IL-23/IL-1βand were reversed by PD-L1 Fc.Taken together,our findings indicate that the PD-1/PD-L1 pathway contributes to the Treg/Th17 imbalance via‘one-two punch’approaches:(i)promoting Th17 cell proliferation,(ii)inhibiting Treg cell differentiation and(iii)enhancing Treg cell plasticity into Th17 cells in PE.The therapeutic value of PD-L1 Fc for PE treatment will be explored in the future.展开更多
In late December 2019,the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which causes coronavirus disease 2019(COVID-19),was identified in Wuhan,China,and the ensuing pandemic has led to more than 5...In late December 2019,the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which causes coronavirus disease 2019(COVID-19),was identified in Wuhan,China,and the ensuing pandemic has led to more than 50 million infected individuals and more than one million deaths by November 10,2020(https://covid19.who.int/).Pathologic investigations of autopsy tissue have focused primarily on the lung,heart,and kidney,whereas morphologic data on testis injury and the effects of SARS-CoV-2 infection on spermatogenesis are limited.Although two groups did not detect SARS-CoV-2 in the semen or testes of recovered COVID-19 patients,1,2 another group confirmed SARS-CoV-2 in the semen of patients.3 Therefore,it is currently unknown whether SARS-CoV-2 infection impacts spermatogenesis and male fertility.In the present study,we evaluated the effects of SARS-CoV-2 infection on spermatogenesis by examining the pathophysiology and molecular features of testes obtained from five male COVID-19 patients at autopsy.展开更多
As the main antibody-producing and antigen-presenting cells,B cells play critical roles in autoimmune diseases,tumors,and transplantation.Recently,the immunoregulatory functions of B cells have attracted attention and...As the main antibody-producing and antigen-presenting cells,B cells play critical roles in autoimmune diseases,tumors,and transplantation.Recently,the immunoregulatory functions of B cells have attracted attention and have been extensively studied in these fields.展开更多
基金This study was supported by research grants from the National Natural Science Foundation of China(NO.81471475).
文摘The programmed cell death-1(PD-1)/PD-ligand 1(PD-L1)pathway is critical for normal pregnancy by promoting regulatory T(Treg)cell development and inhibiting the Th17 response.However,the relationship between the PD-1/PD-L1 pathway and the Treg/Th17 imbalance in pre-eclampsia(PE)is an enigma.In this study,decreased PD-1 and PD-L1 expression and a Treg/Th17 imbalance were observed at the maternal-fetal interface in PE.The regulatory effects of the PD-1/PD-L1 pathway on the Treg and Th17 cell quantities were determined in vitro by targeting T-cell proliferation,differentiation and transdifferentiation.First,decreased PD-1 expression might contribute to a higher Th17 cell frequency by promoting proliferation in PE.Second,the percentages of Treg but not Th17 cells differentiated from peripheral naive CD4+T cells were increased by PD-L1 Fc administration.This effect was accompanied by decreased PI3K/AKT/m-TOR and increased PTEN mRNA expression and was completely reversed by PD-1 blockade.Finally,the percentage of IL-17-producing Treg cells increased and was positively associated with the Th17 cell frequency in PE.Increased RORγt and IL-17 but not Foxp3 and IL-10 mRNA expression by Treg cells was observed with PD-1 blockade.Similar findings occurred when Treg cells were exposed to IL-6/IL-23/IL-1βand were reversed by PD-L1 Fc.Taken together,our findings indicate that the PD-1/PD-L1 pathway contributes to the Treg/Th17 imbalance via‘one-two punch’approaches:(i)promoting Th17 cell proliferation,(ii)inhibiting Treg cell differentiation and(iii)enhancing Treg cell plasticity into Th17 cells in PE.The therapeutic value of PD-L1 Fc for PE treatment will be explored in the future.
基金This work was supported by the Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine,Ferring Pharmaceuticals and Chinese Academy of Sciences(FIRMSCOV02)the Cultivation Plan of International Joint Research Platform of Huazhong University of Science and Technology(5001519009)Emergency Research Funds of Ministry of Science and Technology of P.R.China(2020YFC0844700).
文摘In late December 2019,the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which causes coronavirus disease 2019(COVID-19),was identified in Wuhan,China,and the ensuing pandemic has led to more than 50 million infected individuals and more than one million deaths by November 10,2020(https://covid19.who.int/).Pathologic investigations of autopsy tissue have focused primarily on the lung,heart,and kidney,whereas morphologic data on testis injury and the effects of SARS-CoV-2 infection on spermatogenesis are limited.Although two groups did not detect SARS-CoV-2 in the semen or testes of recovered COVID-19 patients,1,2 another group confirmed SARS-CoV-2 in the semen of patients.3 Therefore,it is currently unknown whether SARS-CoV-2 infection impacts spermatogenesis and male fertility.In the present study,we evaluated the effects of SARS-CoV-2 infection on spermatogenesis by examining the pathophysiology and molecular features of testes obtained from five male COVID-19 patients at autopsy.
基金supported by grants from the National Key Research&Developmental Program of China(2018YFC1003900 and 2018YFC1003904).
文摘As the main antibody-producing and antigen-presenting cells,B cells play critical roles in autoimmune diseases,tumors,and transplantation.Recently,the immunoregulatory functions of B cells have attracted attention and have been extensively studied in these fields.