sirolimus and Rhinitis

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.. 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.. 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.. 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.

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