title: Activated mammalian target of rapamycin is associated with T regulatory cell insufficiency in nasal polyps.
abstract: BACKGROUND
  Decreased infiltration of Foxp3+ T regulatory cell (Treg) is considered to be critical for the Th1/Th2 dysregulation of nasal polyps, while the cellular mechanism underlying Foxp3+ Treg insufficiency is currently not well defined.
  
  
  METHODS
  We attempted to investigate the tissue expression of phosphorylated mammalian target of rapamycin (pmTOR) and infiltration of Foxp3+ Tregs in 28 nasal polyps and 16 controls by histological staining. We also evaluated the effects of blocking the mTOR signaling pathway with rapamycin on T cell phenotype selection and Foxp3+CD4+ Tregs expansion in a tissue culture system.
  
  
  RESULTS
  Significantly increased infiltration of pmTOR+ inflammatory cells and decreased infiltration of Foxp3+CD4+ Tregs into nasal polyps was observed, with an inverse association. In the tissue culture system, we detected significantly elevated Foxp3 expression and IL-10 production, as well as an increased percentage of Foxp3+ Tregs in nasal polyps after blocking the mTOR signaling pathway with rapamycin.
  
  
  CONCLUSIONS
  Here we demonstrate for the first time that the mTOR signaling pathway is associated with Foxp3+ Tregs insufficiency in nasal polyps. Inhibition of the mTOR signaling pathway may be helpful for enhancement of Foxp3+ Treg expansion, as well as modulation of T cell phenotype imbalances in nasal polyps.
authors.affiliation: Allergy and Cancer Center, Otorhinolaryngology Hospital of the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China. entxgfess@163.com
authors.forename: Geng
authors.initials: G
authors.lastname: Xu
authors.forename: Jiahong
authors.initials: J
authors.lastname: Xia
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Hua
authors.forename: Han
authors.initials: H
authors.lastname: Zhou
authors.forename: Chuanzhao
authors.initials: C
authors.lastname: Yu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Kemin
authors.initials: K
authors.lastname: Cai
authors.forename: Jianbo
authors.initials: J
authors.lastname: Shi
authors.forename: Huabin
authors.initials: H
authors.lastname: Li
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000276:immunology / Q000378:metabolism*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D012220:Rhinitis / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012852:Sinusitis / Q000276:immunology / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D020825:T-Box Domain Proteins / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases; D046509:Tissue Culture Techniques; D055815:Young Adult; D000098815:T-bet Transcription Factor
chemical_list: D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D020123:Sirolimus; D020825:T-Box Domain Proteins; D058570:TOR Serine-Threonine Kinases; D000098815:T-bet Transcription Factor; C418974:FOXP3 protein, human; C494749:GATA3 protein, human; C508609:IL10 protein, human; C539900:RORC protein, human; C546842:MTOR protein, human; C494929:PTEN protein, human