Activated mammalian target of rapamycin is associated with T regulatory cell insufficiency in nasal polyps

Respir Res. 2009 Feb 27;10(1):13. doi: 10.1186/1465-9921-10-13.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Female
  • Fluorescent Antibody Technique
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • GATA3 Transcription Factor / metabolism
  • Humans
  • Immunohistochemistry
  • Immunosuppressive Agents / pharmacology
  • Interleukin-10 / metabolism
  • Male
  • Middle Aged
  • Nasal Polyps / immunology
  • Nasal Polyps / metabolism*
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Thyroid Hormone / metabolism
  • Rhinitis / immunology
  • Rhinitis / metabolism*
  • Signal Transduction* / drug effects
  • Sinusitis / immunology
  • Sinusitis / metabolism*
  • Sirolimus / pharmacology
  • T-Box Domain Proteins / metabolism
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • TOR Serine-Threonine Kinases
  • Tissue Culture Techniques
  • Young Adult

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • IL10 protein, human
  • Immunosuppressive Agents
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interleukin-10
  • Protein Kinases
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Sirolimus