BACKGROUND: Antibiotics are widely given for surgical patients to prevent infection. Because of the lack of study on the rational use of antibiotics in patients with human immunodef iciency virus(HIV)-infected during ...BACKGROUND: Antibiotics are widely given for surgical patients to prevent infection. Because of the lack of study on the rational use of antibiotics in patients with human immunodef iciency virus(HIV)-infected during surgical procedures, we analyzed the risk factors affecting postoperative infectious complications in HIV-infected patients and explore the rational use of perioperative antibiotics.METHODS: This retrospective study consisted of 308 HIV-infected patients, 272 males and 36 females, who had undergone operation at the Shanghai Public Health Clinical Center from November 2008 to April 2012. The patients were divided into postoperative infection and non-infection groups. Their age and clinical variables were compared. The correlation between surgical incision, surgical site infection(SSI) and postoperative sepsis was analyzed. Prophylactic antibiotics were used for patients with type I and II incisions for less than 2 days. Patients with type III incisions were given antibiotics until the infection was controlled. Antiretroviral therapy(ART) was prescribed preoperatively for patients whose preoperative CD4 count was <350 cells/μL. For those patients whose preoperative CD4 count was <200 cells/μL, sulfamethoxazole and fluconazole were given preoperatively as prophylactic agents controlling Pneumocystis carinii pneumonia and fungal infection.RESULTS: A total of 196 patients developed postoperative infectious complications, and 7 patients died. Preoperative CD4 counts, ratio of CD4/CD8 cells, hemoglobin level, and postoperative CD4 counts, hemoglobin and albumin levels were risk factors of perioperative infection in HIV-infected patients. Patients with a preoperative CD4 count <200 cell/μL, anemia, a postoperative CD4 count <200 cell/μL or albumin levels <35 g/L were correlated with a higher rate of perioperative infection. There was a signif icant correlation between SSI and the type of surgical incision. The rate of SSI in patients with type I surgical incision was 2% and in those with type II surgical incision was 38%. All the patients who received type III surgical incision developed SSI, and they were more likely to develop postoperative sepsis.CONCLUSIONS: HIV-infected patients are more likely to develop postoperative infectious complications. The rational use of antibiotics in HIV-infected patients could help to reduce the rate of postoperative infectious complications in these patients.展开更多
The heterogeneity and plasticity of T lymphocytes is critical for determining immune response outcomes.Functional regulatory T(Treg)cells are commonly characterized by stable FOXP3 expression and have reported to exhi...The heterogeneity and plasticity of T lymphocytes is critical for determining immune response outcomes.Functional regulatory T(Treg)cells are commonly characterized by stable FOXP3 expression and have reported to exhibit heterogeneous phenotypes under inflammatory conditions.However,the interplay between inflammation and Treg cell suppressive activity still remains elusive.Here,we utilized singlecell RNA sequencing to investigate how human Treg cells respond to the pro-inflammatory cytokine interleukin-6(IL-6).We observed that Treg cells divided into two subpopulations after IL-6 stimulation.TIGITàunstable Treg cells lost FOXP3 expression and gained an effector-like T cell phenotype,whereas TIGIT+Treg cells retained robust suppressive function.Single cell transcriptome analysis revealed a spectrum of cellular states of IL-6-stimulated Treg cells and how cytochrome P450 family 1 subfamily A member 1(CYP1A1)is a crucial regulator of Treg cell suppressive capability and stability.CYP1A1-deficient human Treg cells developed a Th17-like phenotype after IL-6 stimulation.Our findings implicate CYP1A1 as a previously unidentified regulator of Treg cells that may have target potential for clinical application for biotherapies.展开更多
FOXP3＋ regulatory T （Treg） cells are critical in maintaining immune tolerance and homeostasis of the immune system. The molecular mechanisms underlying the stability, plasticity and functional activity of Treg cell...FOXP3＋ regulatory T （Treg） cells are critical in maintaining immune tolerance and homeostasis of the immune system. The molecular mechanisms underlying the stability, plasticity and functional activity of Treg cells have been much studied in recent years. Here, we summarize these intriguing findings, and provide insight into their potential use or manipulation during Treg cell therapy for the treatment of autoimmune diseases, graft-versus-host disease （GVHD） and cancer.展开更多
CD4^+CD25^+regulatory T(Treg)cells express the transcription factor FOXP3 and play an essential role in preventing autoimmunity.Abundant Treg cell accumulation in tumors and tumor draining lymph nodes(TDLNs)has been r...CD4^+CD25^+regulatory T(Treg)cells express the transcription factor FOXP3 and play an essential role in preventing autoimmunity.Abundant Treg cell accumulation in tumors and tumor draining lymph nodes(TDLNs)has been reported to correlate with both poor and favorable prognosis in various cancers,which suggests that Tregs may have multiple effects on antitumor immunity.However,the heterogeneity of tumor-and TDLN-infiltrating Treg cells remains unclear.Here we provide heterogeneity analysis of tumor infiltrating human CD4^+Treg cells and their matched adjacent tissues and TDLNs.We defined three different subpopulations of tumor-and TDLN-infiltrating Treg cells by Helios and CCR8 expression in pancreatic ductal adenocarcinoma(PDAC)and confirmed their functional heterogeneity.Helios^+CCR8^+Treg cells with potent suppressor function and limited IL-2 and IFN-7 secretion were identified in tumors and TDLNs.On the contrary,Helios^-CCR8^-Treg cells have impaired suppressive activity,and elevated expression of pro-inflammatory cytokines.More advanced grades of PDAC have predominantly Helios^+CCR8^+Treg cells and few Helios^-CCR8^-Treg cells both in tumors and TDLNs that suggests poor prognosis.These data could help further define the role of Treg cells and their functional role in tumors and TDLNs.展开更多
Regulatory T(Treg)cells play an essential role in immune homeostasis by controlling the function of various immune effector cells,including RAR-related orphan receptor gammat+(RORγt+)T helper 17(Th17)cells.Foekhead b...Regulatory T(Treg)cells play an essential role in immune homeostasis by controlling the function of various immune effector cells,including RAR-related orphan receptor gammat+(RORγt+)T helper 17(Th17)cells.Foekhead box P3(FoxP3)is the master regulator of Treg cell function,while RORγt is the key transcription factor for the induction of the interleukin(IL)-17 family of cytokines during Th17 cell differentiation.FoxP3 can directly interact with and negatively regulate the function of RORγt,to determine the balance between induced Treg(iTreg)and Th17 cell polarization.Two recent independent studies from the Pan and Chi Labs have shown how hypoxia-inducible factor 1 alpha(HIF1α)is able to tip the balance of T cell differentiation toward the Th17 lineage by responding to the local changes in metabolic shift or an increase in proinflammatory mediators in the microenvironment.By allying with HIF1α,RORγt wins the fight against FoxP3 and Treg cell commitment.展开更多
基金supported by grants from the National Science Foundation of ChinaShanghai Pasteur Foundation+1 种基金Shanghai "Rising Star" program(10QA1407900)Novo Nordisk Chinese Academy of Sciences Foundation
文摘BACKGROUND: Antibiotics are widely given for surgical patients to prevent infection. Because of the lack of study on the rational use of antibiotics in patients with human immunodef iciency virus(HIV)-infected during surgical procedures, we analyzed the risk factors affecting postoperative infectious complications in HIV-infected patients and explore the rational use of perioperative antibiotics.METHODS: This retrospective study consisted of 308 HIV-infected patients, 272 males and 36 females, who had undergone operation at the Shanghai Public Health Clinical Center from November 2008 to April 2012. The patients were divided into postoperative infection and non-infection groups. Their age and clinical variables were compared. The correlation between surgical incision, surgical site infection(SSI) and postoperative sepsis was analyzed. Prophylactic antibiotics were used for patients with type I and II incisions for less than 2 days. Patients with type III incisions were given antibiotics until the infection was controlled. Antiretroviral therapy(ART) was prescribed preoperatively for patients whose preoperative CD4 count was <350 cells/μL. For those patients whose preoperative CD4 count was <200 cells/μL, sulfamethoxazole and fluconazole were given preoperatively as prophylactic agents controlling Pneumocystis carinii pneumonia and fungal infection.RESULTS: A total of 196 patients developed postoperative infectious complications, and 7 patients died. Preoperative CD4 counts, ratio of CD4/CD8 cells, hemoglobin level, and postoperative CD4 counts, hemoglobin and albumin levels were risk factors of perioperative infection in HIV-infected patients. Patients with a preoperative CD4 count <200 cell/μL, anemia, a postoperative CD4 count <200 cell/μL or albumin levels <35 g/L were correlated with a higher rate of perioperative infection. There was a signif icant correlation between SSI and the type of surgical incision. The rate of SSI in patients with type I surgical incision was 2% and in those with type II surgical incision was 38%. All the patients who received type III surgical incision developed SSI, and they were more likely to develop postoperative sepsis.CONCLUSIONS: HIV-infected patients are more likely to develop postoperative infectious complications. The rational use of antibiotics in HIV-infected patients could help to reduce the rate of postoperative infectious complications in these patients.
基金supported by grants from the National Natural Science Foundation of China(81830051,31525008,31670911,31800744 and 31961133011)Shanghai Academic Research Leader(16XD1403800)+2 种基金Shenzhen Municipal Government of China(JCYJ20170817145428361)Shanghai Jiao Tong University(SJTU)The Chinese University of Hong Kong(CUHK)Joint Research Collaboration Fundthe Fundamental Research Funds for Central Universities and the Gusu innovation and entrepreneurship leader talent program。
文摘The heterogeneity and plasticity of T lymphocytes is critical for determining immune response outcomes.Functional regulatory T(Treg)cells are commonly characterized by stable FOXP3 expression and have reported to exhibit heterogeneous phenotypes under inflammatory conditions.However,the interplay between inflammation and Treg cell suppressive activity still remains elusive.Here,we utilized singlecell RNA sequencing to investigate how human Treg cells respond to the pro-inflammatory cytokine interleukin-6(IL-6).We observed that Treg cells divided into two subpopulations after IL-6 stimulation.TIGITàunstable Treg cells lost FOXP3 expression and gained an effector-like T cell phenotype,whereas TIGIT+Treg cells retained robust suppressive function.Single cell transcriptome analysis revealed a spectrum of cellular states of IL-6-stimulated Treg cells and how cytochrome P450 family 1 subfamily A member 1(CYP1A1)is a crucial regulator of Treg cell suppressive capability and stability.CYP1A1-deficient human Treg cells developed a Th17-like phenotype after IL-6 stimulation.Our findings implicate CYP1A1 as a previously unidentified regulator of Treg cells that may have target potential for clinical application for biotherapies.
文摘FOXP3＋ regulatory T （Treg） cells are critical in maintaining immune tolerance and homeostasis of the immune system. The molecular mechanisms underlying the stability, plasticity and functional activity of Treg cells have been much studied in recent years. Here, we summarize these intriguing findings, and provide insight into their potential use or manipulation during Treg cell therapy for the treatment of autoimmune diseases, graft-versus-host disease （GVHD） and cancer.
基金supported by National Basic Research Program of China(2014CB541803 and 2014CB541903)the National Science Foundation of China(31525008,81330072,31670911,31370863+1 种基金SMCST 14JC1406100)Shanghai Academic Research Leader(16XD1403800)
文摘CD4^+CD25^+regulatory T(Treg)cells express the transcription factor FOXP3 and play an essential role in preventing autoimmunity.Abundant Treg cell accumulation in tumors and tumor draining lymph nodes(TDLNs)has been reported to correlate with both poor and favorable prognosis in various cancers,which suggests that Tregs may have multiple effects on antitumor immunity.However,the heterogeneity of tumor-and TDLN-infiltrating Treg cells remains unclear.Here we provide heterogeneity analysis of tumor infiltrating human CD4^+Treg cells and their matched adjacent tissues and TDLNs.We defined three different subpopulations of tumor-and TDLN-infiltrating Treg cells by Helios and CCR8 expression in pancreatic ductal adenocarcinoma(PDAC)and confirmed their functional heterogeneity.Helios^+CCR8^+Treg cells with potent suppressor function and limited IL-2 and IFN-7 secretion were identified in tumors and TDLNs.On the contrary,Helios^-CCR8^-Treg cells have impaired suppressive activity,and elevated expression of pro-inflammatory cytokines.More advanced grades of PDAC have predominantly Helios^+CCR8^+Treg cells and few Helios^-CCR8^-Treg cells both in tumors and TDLNs that suggests poor prognosis.These data could help further define the role of Treg cells and their functional role in tumors and TDLNs.
基金funds from NSFC(Grant Nos.30972702 and 31050110129)SMCST09JC1416100,Shanghai Pasteur Foundation,Shanghai“Rising Star”program 10QA1407900,China-Germany PPP program,Novo Nordisk-Chinese Academy of Sciences(NN-CAS)Foundation,CAS“100-talents”program,CAS“International Young Scientist Fellowship”,and the Sanofi-Aventis-Shanghai Institutes for Biological Sciences(SA-SIBS)scholarship program.
文摘Regulatory T(Treg)cells play an essential role in immune homeostasis by controlling the function of various immune effector cells,including RAR-related orphan receptor gammat+(RORγt+)T helper 17(Th17)cells.Foekhead box P3(FoxP3)is the master regulator of Treg cell function,while RORγt is the key transcription factor for the induction of the interleukin(IL)-17 family of cytokines during Th17 cell differentiation.FoxP3 can directly interact with and negatively regulate the function of RORγt,to determine the balance between induced Treg(iTreg)and Th17 cell polarization.Two recent independent studies from the Pan and Chi Labs have shown how hypoxia-inducible factor 1 alpha(HIF1α)is able to tip the balance of T cell differentiation toward the Th17 lineage by responding to the local changes in metabolic shift or an increase in proinflammatory mediators in the microenvironment.By allying with HIF1α,RORγt wins the fight against FoxP3 and Treg cell commitment.
