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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 levels of T cell cytokines in the supernatants of cultured nasal polyps, as determined by ELISA. Significant changes were observed in the levels of IFN-γ, IL-4, IL-5, and IL-10 by multiple comparisons (P < 0.0125 by the ANOVA test and Bonferroni correction) and Rapamycin was shown to enhance IL-10 production in nasal polyps. More Th1/Th2 and less Treg cytokines were demonstrated in nasal polyps (*P < 0.05 by the unpaired t-test for intragroup comparison). After rapamycin treatment, a slight decrease in Th1 and Th2 cytokines, IFN-γ, IL-4, and IL-5 (30%, 47%, and 41%, respectively;**P > 0.05 by the paired t-test for intragroup comparison), and a significant increase in IL-10 were found in nasal polyps (4.4-fold; **P < 0.05 by the paired t-test for intragroup comparison).
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Figure 5: Rapamycin modulates the levels of T cell cytokines in the supernatants of cultured nasal polyps, as determined by ELISA. Significant changes were observed in the levels of IFN-γ, IL-4, IL-5, and IL-10 by multiple comparisons (P < 0.0125 by the ANOVA test and Bonferroni correction) and Rapamycin was shown to enhance IL-10 production in nasal polyps. More Th1/Th2 and less Treg cytokines were demonstrated in nasal polyps (*P < 0.05 by the unpaired t-test for intragroup comparison). After rapamycin treatment, a slight decrease in Th1 and Th2 cytokines, IFN-γ, IL-4, and IL-5 (30%, 47%, and 41%, respectively;**P > 0.05 by the paired t-test for intragroup comparison), and a significant increase in IL-10 were found in nasal polyps (4.4-fold; **P < 0.05 by the paired t-test for intragroup comparison).

Mentions: Given that cytokine profiles reflect committed T cell phenotypes, we examined the contents of different cytokines (IFN-γ for Th1, IL-4 and IL-5 for Th2, and IL-10 for Tregs) in supernatants of the cultured nasal tissues by cytokine-specific ELISA and found significant changes in the levels of IFN-γ, IL-4, IL-5, and IL-10 during multiple comparisons (P < 0.0125 by the ANOVA test and Bonferroni correction). For intragroup comparison, more Th1/Th2 and less Treg cytokines was observed in polyps than in control (Figure 5) (P < 0.05 by the unpaired t-test), confirming that nasal polyps is characterized by mixed types of Th1/Th2 infiltrates and their corresponding cytokine secretions. After rapamycin treatment, a slight decrease in Th1 and Th2 cytokines, IFN-γ, IL-4, and IL-5 (30%, 47%, and 41%, respectively;P > 0.05 by the paired t-test), and a significant increase in IL-10 was found in nasal polyps compared to the untreated polyp tissues (4.4-fold; P < 0.05 by the paired t-test). These findings suggest that blocking mTOR singaling by rapamycin may enhance the function of Foxp3+ Tregs and IL-10 production 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 levels of T cell cytokines in the supernatants of cultured nasal polyps, as determined by ELISA. Significant changes were observed in the levels of IFN-γ, IL-4, IL-5, and IL-10 by multiple comparisons (P < 0.0125 by the ANOVA test and Bonferroni correction) and Rapamycin was shown to enhance IL-10 production in nasal polyps. More Th1/Th2 and less Treg cytokines were demonstrated in nasal polyps (*P < 0.05 by the unpaired t-test for intragroup comparison). After rapamycin treatment, a slight decrease in Th1 and Th2 cytokines, IFN-γ, IL-4, and IL-5 (30%, 47%, and 41%, respectively;**P > 0.05 by the paired t-test for intragroup comparison), and a significant increase in IL-10 were found in nasal polyps (4.4-fold; **P < 0.05 by the paired t-test for intragroup comparison).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Rapamycin modulates the levels of T cell cytokines in the supernatants of cultured nasal polyps, as determined by ELISA. Significant changes were observed in the levels of IFN-γ, IL-4, IL-5, and IL-10 by multiple comparisons (P < 0.0125 by the ANOVA test and Bonferroni correction) and Rapamycin was shown to enhance IL-10 production in nasal polyps. More Th1/Th2 and less Treg cytokines were demonstrated in nasal polyps (*P < 0.05 by the unpaired t-test for intragroup comparison). After rapamycin treatment, a slight decrease in Th1 and Th2 cytokines, IFN-γ, IL-4, and IL-5 (30%, 47%, and 41%, respectively;**P > 0.05 by the paired t-test for intragroup comparison), and a significant increase in IL-10 were found in nasal polyps (4.4-fold; **P < 0.05 by the paired t-test for intragroup comparison).
Mentions: Given that cytokine profiles reflect committed T cell phenotypes, we examined the contents of different cytokines (IFN-γ for Th1, IL-4 and IL-5 for Th2, and IL-10 for Tregs) in supernatants of the cultured nasal tissues by cytokine-specific ELISA and found significant changes in the levels of IFN-γ, IL-4, IL-5, and IL-10 during multiple comparisons (P < 0.0125 by the ANOVA test and Bonferroni correction). For intragroup comparison, more Th1/Th2 and less Treg cytokines was observed in polyps than in control (Figure 5) (P < 0.05 by the unpaired t-test), confirming that nasal polyps is characterized by mixed types of Th1/Th2 infiltrates and their corresponding cytokine secretions. After rapamycin treatment, a slight decrease in Th1 and Th2 cytokines, IFN-γ, IL-4, and IL-5 (30%, 47%, and 41%, respectively;P > 0.05 by the paired t-test), and a significant increase in IL-10 was found in nasal polyps compared to the untreated polyp tissues (4.4-fold; P < 0.05 by the paired t-test). These findings suggest that blocking mTOR singaling by rapamycin may enhance the function of Foxp3+ Tregs and IL-10 production 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