Diminished levels of regulatory T cell subsets (CD8 Foxp3, CD4 Foxp3 and CD4 CD39 Foxp3) but increased Foxp3 expression in adipose tissue from overweight subjects
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Objectives The aim of this study was to identify regulatory T cell (Treg) subsets residing in adipose tissue, demonstrate their immunosuppressive functions, and assess the possible role of Sirt1 in their function in overweight subjects. Methods Fat samples were obtained by lipoaspiration from healthy overweight (n = 15) and normoweight (n = 11) subjects. We obtained the stromal vascular fraction and then isolated the mononuclear cells by Ficoll-Hypaque sedimentation. The Treg subsets were analyzed by flow cytometry, the expression of Sirt1 and Foxp3 was detected by western blot, and peroxisome proliferator-activated receptor gamma (PPAR-γ) expression was evaluated by qPCR. Results We detected low numbers of Treg cell subsets displaying the phenotypes CD4 CD25−Foxp3 , CD8 CD25−Foxp3 , and CD4 CD39 Foxp3 associated with increased body mass index in overweight subjects. We found lower levels of mRNA SIRT1 expression in adipocytes from overweight subjects than in those from normoweight subjects. In contrast, increased amounts of the Sirt1 and Foxp3 proteins in adipose tissue mononuclear cells from overweight subjects were observed. The immunosuppressive function of CD4 CD25 Treg cells is higher in cells from obese subject than in those from normoweight subject. Conclusions Low levels of Treg subsets in overweight subjects with a high percentage of inhibition of proliferation could be related to high levels of the Foxp3 protein. Likewise, the low expression of SIRT1 and PPAR-γ mRNA levels and increased concentration of Sirt1 proteins allows adipose tissue mononuclear cells to respond to stimuli dependent on adenosine receptors and sirtuin pathways. © 2016 Elsevier Inc.
Objectives The aim of this study was to identify regulatory T cell (Treg) subsets residing in adipose tissue, demonstrate their immunosuppressive functions, and assess the possible role of Sirt1 in their function in overweight subjects. Methods Fat samples were obtained by lipoaspiration from healthy overweight (n = 15) and normoweight (n = 11) subjects. We obtained the stromal vascular fraction and then isolated the mononuclear cells by Ficoll-Hypaque sedimentation. The Treg subsets were analyzed by flow cytometry, the expression of Sirt1 and Foxp3 was detected by western blot, and peroxisome proliferator-activated receptor gamma (PPAR-γ) expression was evaluated by qPCR. Results We detected low numbers of Treg cell subsets displaying the phenotypes CD4%2bCD25−Foxp3%2b, CD8%2bCD25−Foxp3%2b, and CD4%2bCD39%2bFoxp3%2b associated with increased body mass index in overweight subjects. We found lower levels of mRNA SIRT1 expression in adipocytes from overweight subjects than in those from normoweight subjects. In contrast, increased amounts of the Sirt1 and Foxp3 proteins in adipose tissue mononuclear cells from overweight subjects were observed. The immunosuppressive function of CD4%2bCD25%2b Treg cells is higher in cells from obese subject than in those from normoweight subject. Conclusions Low levels of Treg subsets in overweight subjects with a high percentage of inhibition of proliferation could be related to high levels of the Foxp3 protein. Likewise, the low expression of SIRT1 and PPAR-γ mRNA levels and increased concentration of Sirt1 proteins allows adipose tissue mononuclear cells to respond to stimuli dependent on adenosine receptors and sirtuin pathways. © 2016 Elsevier Inc.
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Foxp3; Infiltrated lymphocytes; Overweight; PPAR-γ; Sirt1; Treg cells messenger RNA; peroxisome proliferator activated receptor gamma; sirtuin 1; transcription factor FOXP3; apyrase; CD39 antigen; forkhead transcription factor; FOXP3 protein, human; leukocyte antigen; peroxisome proliferator activated receptor gamma; SIRT1 protein, human; sirtuin 1; adipose tissue; adult; Article; body mass; CD4 CD25 T lymphocyte; CD4 CD39 Foxp3 T lymphocyte; CD4 Foxp3 T lymphocyte; CD4 T lymphocyte; CD8 Foxp3 T lymphocyte; CD8 T lymphocyte; cell proliferation; clinical article; controlled study; female; flow cytometry; human; human cell; human tissue; immunosuppressive treatment; mononuclear cell; obesity; phenotype; polymerase chain reaction; priority journal; protein expression; protein function; regulatory T lymphocyte; Western blotting; adipose tissue; CD4 lymphocyte count; genetics; male; metabolism; obesity; regulatory T lymphocyte; T lymphocyte subpopulation; Adipose Tissue; Adult; Antigens, CD; Apyrase; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes; Female; Flow Cytometry; Forkhead Transcription Factors; Humans; Male; Overweight; PPAR gamma; Sirtuin 1; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory
Foxp3; Infiltrated lymphocytes; Overweight; PPAR-γ; Sirt1; Treg cells messenger RNA; peroxisome proliferator activated receptor gamma; sirtuin 1; transcription factor FOXP3; apyrase; CD39 antigen; forkhead transcription factor; FOXP3 protein, human; leukocyte antigen; peroxisome proliferator activated receptor gamma; SIRT1 protein, human; sirtuin 1; adipose tissue; adult; Article; body mass; CD4+ CD25+ T lymphocyte; CD4+ CD39+ Foxp3+ T lymphocyte; CD4+ Foxp3+ T lymphocyte; CD4+ T lymphocyte; CD8+ Foxp3+ T lymphocyte; CD8+ T lymphocyte; cell proliferation; clinical article; controlled study; female; flow cytometry; human; human cell; human tissue; immunosuppressive treatment; mononuclear cell; obesity; phenotype; polymerase chain reaction; priority journal; protein expression; protein function; regulatory T lymphocyte; Western blotting; adipose tissue; CD4 lymphocyte count; genetics; male; metabolism; obesity; regulatory T lymphocyte; T lymphocyte subpopulation; Adipose Tissue; Adult; Antigens, CD; Apyrase; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes; Female; Flow Cytometry; Forkhead Transcription Factors; Humans; Male; Overweight; PPAR gamma; Sirtuin 1; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory
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