title: [Depressive effect of cigarette smoke extracts on dendritic cells inducing differentiation of CD4+T cells into CD4+CD25+Foxp3+ Tregs].
abstract: OBJECTIVE
  To explore the impact of both cigarette smoke extracts (CSE) and CD40-CD40L pathway blocking on mouse myeloid dendritic cells (DCs) inducing CD4(+)T cells differentiation into CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs). METHODS :A combination of recombinant mouse granulocyte-macrophage colony stimulating factor (rmGM-CSF, 40 ng/mL) and recombinant mouse IL-4 (rmIL-4, 10 ng/mL) was applied in vitro to induce the differentiation of BALB/c mouse myeloid monocytes into DCs. DCs were detected for the expression of CD40 molecules through flow cytometry. CD4(+)T cells were sorted out from BALB/c mouse spleen cells with magnetic activated cell sorting technique. Myeloid DCs were co-cultivated with CD4(+)T cells separated from the control-group for 24 hours in the presence of CSE or antagonistic CD40 antibody. CD4(+)CD25(+)Foxp3(+)Tregs were quantified with flow cytometry, and concentrations of IL-10 and IL-6 in cell supernatants were detected with liquid phase chip technology.
  
  
  RESULTS
  The co-cultivation of DCs and CD4(+)T cells promoted CD4(+)CD25(+)Foxp3(+)Tregs differentiation. However, after stimulated by CSE, the number of CD4(+)CD25(+)Foxp3(+)Tregs differentiated by co-cultivation of DCs and CD4(+)T cells was reduced, accompanied by the decrease of IL-10 concentration and the increased of IL-6 concentration. In contrast, with the intervention of antagonistic CD40 antibody, the number of CD4(+)CD25(+)Foxp3(+)Tregs increased, IL-10 concentration rose and IL-6 dropped.
  
  
  CONCLUSIONS
  CSE can substantially reduce CD4(+)CD25(+)Foxp3(+)Tregs, but blocking CD40-CD40L pathway in vitro by antagonistic CD40 antibody can promote the process of CD4(+)T cells differentiating into CD4(+)CD25(+)Foxp3(+)Tregs.
authors.affiliation: The Department of Respiratory Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liang
authors.affiliation: The Department of Respiratory Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Zhou
authors.affiliation: The Department of Respiratory Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Longju
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Department of Respiratory Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: The Department of Respiratory Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China. *Corresponding author, E-mail: xnzhong101@sina.com.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019013:CD40 Antigens / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008807:Mice, Inbred BALB C; D012906:Smoke; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014026:Nicotiana / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000906:Antibodies; D019013:CD40 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D012906:Smoke; D016753:Interleukin-10