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

Xu G, Xia J, Hua X, Zhou H, Yu C, Liu Z, Cai K, Shi J, Li H - Respir. Res. (2009)

Bottom Line: 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.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Allergy and Cancer Center, Otorhinolaryngology Hospital of the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China. entxgfess@163.com

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.

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Rapamycin modulates the relative levels of T-bet, GATA-3, Foxp3, and RORγt mRNA in cultured nasal polyps, as determined by real time RT-PCR. Rapamycin stimulation has been shown to be associated with the expression of Foxp3 mRNA in nasal polyps. Elevated T-bet and GATA-3 mRNA and decreased Foxp3 mRNA were observed in nasal polyps (* P < 0.05 by the unpaired t-test for intergroup comparison) (A-C). After treatment with rapamycin, Foxp3 mRNA increased significantly in nasal polyps as well as in controls (5.5-fold and 2.7-fold, respectively) (**P < 0.05 by the paired t-test for intragroup comparison), whereas T-bet and GATA-3 mRNAs decreased significantly in nasal polyps (42% and 56%, respectively) (**P < 0.05 by paired t-test intra-group comparison). No significant changes in RORγt gene expression were found by multiple comparisons (D) (P > 0.0125 by the ANOVA test and Bonferroni correction).
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Figure 2: Rapamycin modulates the relative levels of T-bet, GATA-3, Foxp3, and RORγt mRNA in cultured nasal polyps, as determined by real time RT-PCR. Rapamycin stimulation has been shown to be associated with the expression of Foxp3 mRNA in nasal polyps. Elevated T-bet and GATA-3 mRNA and decreased Foxp3 mRNA were observed in nasal polyps (* P < 0.05 by the unpaired t-test for intergroup comparison) (A-C). After treatment with rapamycin, Foxp3 mRNA increased significantly in nasal polyps as well as in controls (5.5-fold and 2.7-fold, respectively) (**P < 0.05 by the paired t-test for intragroup comparison), whereas T-bet and GATA-3 mRNAs decreased significantly in nasal polyps (42% and 56%, respectively) (**P < 0.05 by paired t-test intra-group comparison). No significant changes in RORγt gene expression were found by multiple comparisons (D) (P > 0.0125 by the ANOVA test and Bonferroni correction).

Mentions: Since the functional development of T cells is regulated by specific transcription factors, we quantified the levels of T-bet, GATA-3, Foxp3, and RORγt mRNA in rapamycin-stimulated nasal polyps by real time RT-PCR. As shown in Figure 2, the expression of T-bet, GATA-3, Foxp3, and RORγt mRNA was detected in all specimens, and significant changes in T-bet, GATA-3, and Foxp3 gene expression were observed during multiple comparisons (P < 0.0125 by the ANOVA test and Bonferroni correction). For intragroup comparison, we observed a significant elevation of T-bet and GATA-3 mRNA, but a significant reduction of Foxp3 mRNA in nasal polyps compared to the control mucosa (P < 0.05 by the unpaired t-test). After stimulation with rapamycin at a final concentration of 10 nM for 48 h, we found that Foxp3 mRNA was increased significantly in nasal polyps, as well as in the control (5.5-fold and 2.7-fold, respectively) (P < 0.05 by the paired t-test), whereas T-bet and GATA-3 mRNAs were significantly decreased in nasal polyps (42% and 56%, respectively) (P < 0.05 by the paired t-test). However, there was no significant change in RORγt gene expression during multiple comparisons (P > 0.0125 by the ANOVA test and Bonferroni correction). Therefore, our results provide evidence that rapamycin stimulation is associated with Foxp3 mRNA expression in nasal polyps.


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

Xu G, Xia J, Hua X, Zhou H, Yu C, Liu Z, Cai K, Shi J, Li H - Respir. Res. (2009)

Rapamycin modulates the relative levels of T-bet, GATA-3, Foxp3, and RORγt mRNA in cultured nasal polyps, as determined by real time RT-PCR. Rapamycin stimulation has been shown to be associated with the expression of Foxp3 mRNA in nasal polyps. Elevated T-bet and GATA-3 mRNA and decreased Foxp3 mRNA were observed in nasal polyps (* P < 0.05 by the unpaired t-test for intergroup comparison) (A-C). After treatment with rapamycin, Foxp3 mRNA increased significantly in nasal polyps as well as in controls (5.5-fold and 2.7-fold, respectively) (**P < 0.05 by the paired t-test for intragroup comparison), whereas T-bet and GATA-3 mRNAs decreased significantly in nasal polyps (42% and 56%, respectively) (**P < 0.05 by paired t-test intra-group comparison). No significant changes in RORγt gene expression were found by multiple comparisons (D) (P > 0.0125 by the ANOVA test and Bonferroni correction).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651851&req=5

Figure 2: Rapamycin modulates the relative levels of T-bet, GATA-3, Foxp3, and RORγt mRNA in cultured nasal polyps, as determined by real time RT-PCR. Rapamycin stimulation has been shown to be associated with the expression of Foxp3 mRNA in nasal polyps. Elevated T-bet and GATA-3 mRNA and decreased Foxp3 mRNA were observed in nasal polyps (* P < 0.05 by the unpaired t-test for intergroup comparison) (A-C). After treatment with rapamycin, Foxp3 mRNA increased significantly in nasal polyps as well as in controls (5.5-fold and 2.7-fold, respectively) (**P < 0.05 by the paired t-test for intragroup comparison), whereas T-bet and GATA-3 mRNAs decreased significantly in nasal polyps (42% and 56%, respectively) (**P < 0.05 by paired t-test intra-group comparison). No significant changes in RORγt gene expression were found by multiple comparisons (D) (P > 0.0125 by the ANOVA test and Bonferroni correction).
Mentions: Since the functional development of T cells is regulated by specific transcription factors, we quantified the levels of T-bet, GATA-3, Foxp3, and RORγt mRNA in rapamycin-stimulated nasal polyps by real time RT-PCR. As shown in Figure 2, the expression of T-bet, GATA-3, Foxp3, and RORγt mRNA was detected in all specimens, and significant changes in T-bet, GATA-3, and Foxp3 gene expression were observed during multiple comparisons (P < 0.0125 by the ANOVA test and Bonferroni correction). For intragroup comparison, we observed a significant elevation of T-bet and GATA-3 mRNA, but a significant reduction of Foxp3 mRNA in nasal polyps compared to the control mucosa (P < 0.05 by the unpaired t-test). After stimulation with rapamycin at a final concentration of 10 nM for 48 h, we found that Foxp3 mRNA was increased significantly in nasal polyps, as well as in the control (5.5-fold and 2.7-fold, respectively) (P < 0.05 by the paired t-test), whereas T-bet and GATA-3 mRNAs were significantly decreased in nasal polyps (42% and 56%, respectively) (P < 0.05 by the paired t-test). However, there was no significant change in RORγt gene expression during multiple comparisons (P > 0.0125 by the ANOVA test and Bonferroni correction). Therefore, our results provide evidence that rapamycin stimulation is associated with Foxp3 mRNA expression in nasal polyps.

Bottom Line: 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.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Allergy and Cancer Center, Otorhinolaryngology Hospital of the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China. entxgfess@163.com

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.

Show MeSH
Related in: MedlinePlus