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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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Transgenic expression of IL-23R enhanced Th17 while inhibited Th1 differentiation in vitro(A) Generation of IL-23R Tg mice. IL-23R was driven by an hCD2 promoter under the control of hCD2 LCR. IL-23R mRNA expression was tested in 2 lines. (B-C) Naïve T cells were FACS-sorted from IL-23R Tg or B6 mice and activated under Th17 and Th1 conditions with or without recombinant mouse IL-23. 4 days later, IFN-γ and IL-17 producing cells were analyzed by intracellular staining. Numbers within the quadrants indicate the percentage of positive cells. Data shown represent as least 2 independent experiments with consistent results.
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Figure 3: Transgenic expression of IL-23R enhanced Th17 while inhibited Th1 differentiation in vitro(A) Generation of IL-23R Tg mice. IL-23R was driven by an hCD2 promoter under the control of hCD2 LCR. IL-23R mRNA expression was tested in 2 lines. (B-C) Naïve T cells were FACS-sorted from IL-23R Tg or B6 mice and activated under Th17 and Th1 conditions with or without recombinant mouse IL-23. 4 days later, IFN-γ and IL-17 producing cells were analyzed by intracellular staining. Numbers within the quadrants indicate the percentage of positive cells. Data shown represent as least 2 independent experiments with consistent results.

Mentions: Since IL-23 influences airway inflammation in a Th17-independent manner, we then asked whether IL-23 functions through T cells in regulation of airway inflammation. First, we generated two lines of IL-23R transgenic mice with IL-23R overexpression in T cells using human CD2 mini locus 27 (Fig. 3A). One of the two lines (Line 2) was extensively analyzed. Next, we verified the function of IL-23R transgene (Tg) during Th17 cell differenciation. Naïve CD4+ T cells from IL-23R Tg mice or their littermate control were differentiated to Th17 cells in the presence or absence of recombinant mouse IL-23. Under the Th17 condition, addition of IL-23 significantly increased the frequency IL-17-producing T cells in IL-23R Tg T cells (Figure. 3B). Furthermore, under the Th1 condition, addition of IL-23 greatly inhibited IFN-γ-producing T cells in IL-23R Tg T cells (Figure. 3C). Thus, transgenic overexpression of IL-23R enhances Th17 but inhibits Th1 differentiation.


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

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

Transgenic expression of IL-23R enhanced Th17 while inhibited Th1 differentiation in vitro(A) Generation of IL-23R Tg mice. IL-23R was driven by an hCD2 promoter under the control of hCD2 LCR. IL-23R mRNA expression was tested in 2 lines. (B-C) Naïve T cells were FACS-sorted from IL-23R Tg or B6 mice and activated under Th17 and Th1 conditions with or without recombinant mouse IL-23. 4 days later, IFN-γ and IL-17 producing cells were analyzed by intracellular staining. Numbers within the quadrants indicate the percentage of positive cells. Data shown represent as least 2 independent experiments with consistent results.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Transgenic expression of IL-23R enhanced Th17 while inhibited Th1 differentiation in vitro(A) Generation of IL-23R Tg mice. IL-23R was driven by an hCD2 promoter under the control of hCD2 LCR. IL-23R mRNA expression was tested in 2 lines. (B-C) Naïve T cells were FACS-sorted from IL-23R Tg or B6 mice and activated under Th17 and Th1 conditions with or without recombinant mouse IL-23. 4 days later, IFN-γ and IL-17 producing cells were analyzed by intracellular staining. Numbers within the quadrants indicate the percentage of positive cells. Data shown represent as least 2 independent experiments with consistent results.
Mentions: Since IL-23 influences airway inflammation in a Th17-independent manner, we then asked whether IL-23 functions through T cells in regulation of airway inflammation. First, we generated two lines of IL-23R transgenic mice with IL-23R overexpression in T cells using human CD2 mini locus 27 (Fig. 3A). One of the two lines (Line 2) was extensively analyzed. Next, we verified the function of IL-23R transgene (Tg) during Th17 cell differenciation. Naïve CD4+ T cells from IL-23R Tg mice or their littermate control were differentiated to Th17 cells in the presence or absence of recombinant mouse IL-23. Under the Th17 condition, addition of IL-23 significantly increased the frequency IL-17-producing T cells in IL-23R Tg T cells (Figure. 3B). Furthermore, under the Th1 condition, addition of IL-23 greatly inhibited IFN-γ-producing T cells in IL-23R Tg T cells (Figure. 3C). Thus, transgenic overexpression of IL-23R enhances Th17 but inhibits Th1 differentiation.

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