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IL-23 signaling enhances Th2 polarization and regulates allergic airway inflammation.

Peng J, Yang XO, Chang SH, Yang J, Dong C - Cell Res. (2009)

Bottom Line: In vitro, IL-23-IL-23R signaling promoted GATA-3 expression and enhanced Th2 cytokine expression.Conversely, in the absence of this signal, Th2 cell differentiation was partially inhibited.Therefore, IL-23 signaling may regulate allergic asthma through modulation of Th2 cell differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.

ABSTRACT
IL-23/IL-17 axis is an important regulator in various inflammatory diseases. However, the role of IL-23 in allergic airway inflammation is not well understood. In this study, we show that in an allergen-induced asthma model, mice with transgenic overexpression of IL-23R exhibited increased airway infiltration of eosinophils and Th2 cytokine production, whereas those deficient in IL-23 displayed reduced airway inflammation. In vitro, IL-23-IL-23R signaling promoted GATA-3 expression and enhanced Th2 cytokine expression. Conversely, in the absence of this signal, Th2 cell differentiation was partially inhibited. Therefore, IL-23 signaling may regulate allergic asthma through modulation of Th2 cell differentiation.

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IL-23-IL-23R signaling promotes Th2 differenciation in vitroNaïve T cells were FACS-sorted from IL-23R Tg or B6 mice and stimulated with anti-CD3 and anti-CD28 in the presence of IL-2, IL-4, anti- IFN-γ. (A) 5 days later, IL-4 and IL-17 producing cells were analyzed by intracellular staining. Numbers within the quadrants indicate the percentage of positive cells. (B) Cytokine production was measured by ELISA. (C) T-bet, GATA3 and Foxp3 mRNA expression was analyzed by quatitative realtime RT-PCR. (B–C) The data are expressed as the mean ± SD of triplicate samples. Student t test, *, p < 0.05; p values were calculated from 2–3 independent experiments with consistent results.
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Figure 6: IL-23-IL-23R signaling promotes Th2 differenciation in vitroNaïve T cells were FACS-sorted from IL-23R Tg or B6 mice and stimulated with anti-CD3 and anti-CD28 in the presence of IL-2, IL-4, anti- IFN-γ. (A) 5 days later, IL-4 and IL-17 producing cells were analyzed by intracellular staining. Numbers within the quadrants indicate the percentage of positive cells. (B) Cytokine production was measured by ELISA. (C) T-bet, GATA3 and Foxp3 mRNA expression was analyzed by quatitative realtime RT-PCR. (B–C) The data are expressed as the mean ± SD of triplicate samples. Student t test, *, p < 0.05; p values were calculated from 2–3 independent experiments with consistent results.

Mentions: To rule out the possibility of IL-23 acting on APCs, we utilized an APC-free system. Naïve CD4+ T cells from IL-23R Tg mice or their littermate controls were activated with plate-bound anti-CD3 and anti-CD28 in the presence or absence of recombinant mouse IL-23. Addition of IL-23 increased IL-4-producing cell numbers and protein expression of IL-4 and IL-13 in IL-23R Tg cells (Fig. 6A-B). In WT T cells, only IL-13 was significantly enhanced by IL-23 treatment (Fig. 6A-B). Consistently, in response to IL-23 stimulation, IL-23R Tg but not WT T cells highly expressed GATA-3 mRNA (Fig. 6C). Taken together, the IL-23-IL-23R signaling can promote Th2 differentiation through direct action with CD4+ T cells.


IL-23 signaling enhances Th2 polarization and regulates allergic airway inflammation.

Peng J, Yang XO, Chang SH, Yang J, Dong C - Cell Res. (2009)

IL-23-IL-23R signaling promotes Th2 differenciation in vitroNaïve T cells were FACS-sorted from IL-23R Tg or B6 mice and stimulated with anti-CD3 and anti-CD28 in the presence of IL-2, IL-4, anti- IFN-γ. (A) 5 days later, IL-4 and IL-17 producing cells were analyzed by intracellular staining. Numbers within the quadrants indicate the percentage of positive cells. (B) Cytokine production was measured by ELISA. (C) T-bet, GATA3 and Foxp3 mRNA expression was analyzed by quatitative realtime RT-PCR. (B–C) The data are expressed as the mean ± SD of triplicate samples. Student t test, *, p < 0.05; p values were calculated from 2–3 independent experiments with consistent results.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2801763&req=5

Figure 6: IL-23-IL-23R signaling promotes Th2 differenciation in vitroNaïve T cells were FACS-sorted from IL-23R Tg or B6 mice and stimulated with anti-CD3 and anti-CD28 in the presence of IL-2, IL-4, anti- IFN-γ. (A) 5 days later, IL-4 and IL-17 producing cells were analyzed by intracellular staining. Numbers within the quadrants indicate the percentage of positive cells. (B) Cytokine production was measured by ELISA. (C) T-bet, GATA3 and Foxp3 mRNA expression was analyzed by quatitative realtime RT-PCR. (B–C) The data are expressed as the mean ± SD of triplicate samples. Student t test, *, p < 0.05; p values were calculated from 2–3 independent experiments with consistent results.
Mentions: To rule out the possibility of IL-23 acting on APCs, we utilized an APC-free system. Naïve CD4+ T cells from IL-23R Tg mice or their littermate controls were activated with plate-bound anti-CD3 and anti-CD28 in the presence or absence of recombinant mouse IL-23. Addition of IL-23 increased IL-4-producing cell numbers and protein expression of IL-4 and IL-13 in IL-23R Tg cells (Fig. 6A-B). In WT T cells, only IL-13 was significantly enhanced by IL-23 treatment (Fig. 6A-B). Consistently, in response to IL-23 stimulation, IL-23R Tg but not WT T cells highly expressed GATA-3 mRNA (Fig. 6C). Taken together, the IL-23-IL-23R signaling can promote Th2 differentiation through direct action with CD4+ T cells.

Bottom Line: In vitro, IL-23-IL-23R signaling promoted GATA-3 expression and enhanced Th2 cytokine expression.Conversely, in the absence of this signal, Th2 cell differentiation was partially inhibited.Therefore, IL-23 signaling may regulate allergic asthma through modulation of Th2 cell differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.

ABSTRACT
IL-23/IL-17 axis is an important regulator in various inflammatory diseases. However, the role of IL-23 in allergic airway inflammation is not well understood. In this study, we show that in an allergen-induced asthma model, mice with transgenic overexpression of IL-23R exhibited increased airway infiltration of eosinophils and Th2 cytokine production, whereas those deficient in IL-23 displayed reduced airway inflammation. In vitro, IL-23-IL-23R signaling promoted GATA-3 expression and enhanced Th2 cytokine expression. Conversely, in the absence of this signal, Th2 cell differentiation was partially inhibited. Therefore, IL-23 signaling may regulate allergic asthma through modulation of Th2 cell differentiation.

Show MeSH
Related in: MedlinePlus