Limits...
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.

Show MeSH

Related in: MedlinePlus

Rapamycin increases the percentages of Tregs in cultured nasal polyps analyzed by flow cytometry. Representative two-dimension scatter diagrams of CD4, CD25, and Foxp3 are shown (A) and we found that rapamycin treatment is associated with an increase in Foxp3+ Tregs in cultured nasal polyps(B). Significant changes in CD4+CD25+ and Foxp3+CD4+ cells were observed during multiple comparisons (P < 0.0125 by the ANOVA test and Bonferroni correction). The percentages of CD4+CD25+ and Foxp3+CD4+ cells significantly were decreased in nasal polyps, compared to the control (Figure 3) (*P < 0.05 by the unpaired t-test for intergroup comparison). After treatment with rapamycin, a significant increase in the frequencies of CD4+CD25+ cells and Foxp3+CD4+ Tregs was found in nasal polyps (**P < 0.05 by the paired t-test for intragroup comparison).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2651851&req=5

Figure 3: Rapamycin increases the percentages of Tregs in cultured nasal polyps analyzed by flow cytometry. Representative two-dimension scatter diagrams of CD4, CD25, and Foxp3 are shown (A) and we found that rapamycin treatment is associated with an increase in Foxp3+ Tregs in cultured nasal polyps(B). Significant changes in CD4+CD25+ and Foxp3+CD4+ cells were observed during multiple comparisons (P < 0.0125 by the ANOVA test and Bonferroni correction). The percentages of CD4+CD25+ and Foxp3+CD4+ cells significantly were decreased in nasal polyps, compared to the control (Figure 3) (*P < 0.05 by the unpaired t-test for intergroup comparison). After treatment with rapamycin, a significant increase in the frequencies of CD4+CD25+ cells and Foxp3+CD4+ Tregs was found in nasal polyps (**P < 0.05 by the paired t-test for intragroup comparison).

Mentions: In order to evaluate the frequency of Foxp3+ Tregs in nasal polyps after rapamycin treatment, we examined CD4, CD25, and Foxp3 biomarkers in isolated cells from nasal polyps by flow cytometric analysis. Significant changes in CD4+CD25+ and Foxp3+CD4+ cells were observed by multiple comparisons (P < 0.0125 by ANOVA test and Bonferroni correction). For intragroup comparison, we found the percentages of CD4+CD25+ and Foxp3+CD4+ cells to be significantly decreased in nasal polyps compared to the control (Figure 3) (P < 0.05 by the unpaired t-test). After treatment with rapamycin, a significant increase in the frequencies of CD4+CD25+ cells and Foxp3+CD4+ Tregs in nasal polyps was found compared to untreated nasal polyps (P < 0.05 by the paired t-test). Thus, our results show that rapamycin administration is associated with elevated Foxp3+ Tregs in cultured 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 increases the percentages of Tregs in cultured nasal polyps analyzed by flow cytometry. Representative two-dimension scatter diagrams of CD4, CD25, and Foxp3 are shown (A) and we found that rapamycin treatment is associated with an increase in Foxp3+ Tregs in cultured nasal polyps(B). Significant changes in CD4+CD25+ and Foxp3+CD4+ cells were observed during multiple comparisons (P < 0.0125 by the ANOVA test and Bonferroni correction). The percentages of CD4+CD25+ and Foxp3+CD4+ cells significantly were decreased in nasal polyps, compared to the control (Figure 3) (*P < 0.05 by the unpaired t-test for intergroup comparison). After treatment with rapamycin, a significant increase in the frequencies of CD4+CD25+ cells and Foxp3+CD4+ Tregs was found in nasal polyps (**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 3: Rapamycin increases the percentages of Tregs in cultured nasal polyps analyzed by flow cytometry. Representative two-dimension scatter diagrams of CD4, CD25, and Foxp3 are shown (A) and we found that rapamycin treatment is associated with an increase in Foxp3+ Tregs in cultured nasal polyps(B). Significant changes in CD4+CD25+ and Foxp3+CD4+ cells were observed during multiple comparisons (P < 0.0125 by the ANOVA test and Bonferroni correction). The percentages of CD4+CD25+ and Foxp3+CD4+ cells significantly were decreased in nasal polyps, compared to the control (Figure 3) (*P < 0.05 by the unpaired t-test for intergroup comparison). After treatment with rapamycin, a significant increase in the frequencies of CD4+CD25+ cells and Foxp3+CD4+ Tregs was found in nasal polyps (**P < 0.05 by the paired t-test for intragroup comparison).
Mentions: In order to evaluate the frequency of Foxp3+ Tregs in nasal polyps after rapamycin treatment, we examined CD4, CD25, and Foxp3 biomarkers in isolated cells from nasal polyps by flow cytometric analysis. Significant changes in CD4+CD25+ and Foxp3+CD4+ cells were observed by multiple comparisons (P < 0.0125 by ANOVA test and Bonferroni correction). For intragroup comparison, we found the percentages of CD4+CD25+ and Foxp3+CD4+ cells to be significantly decreased in nasal polyps compared to the control (Figure 3) (P < 0.05 by the unpaired t-test). After treatment with rapamycin, a significant increase in the frequencies of CD4+CD25+ cells and Foxp3+CD4+ Tregs in nasal polyps was found compared to untreated nasal polyps (P < 0.05 by the paired t-test). Thus, our results show that rapamycin administration is associated with elevated Foxp3+ Tregs in cultured 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