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. 2025 Dec;11(1):2541503.
doi: 10.1080/20565623.2025.2541503. Epub 2025 Aug 1.

GATA3 regulates Th1/Th2 balance in allergic rhinitis by interacting with RUNX1

Yuxiao Li  1   2 , Tianrong Wang  1 , Ming He  3 , Yu Wang  1 , Jiayan He  1
Affiliations

GATA3 regulates Th1/Th2 balance in allergic rhinitis by interacting with RUNX1

Yuxiao Li et al. Future Sci OA. 2025 Dec.

Abstract

Objective: To investigate the action mechanism of GATA3 and Runt-related transcription factor 1(RUNX1) in modulating regulatory the Th1/Th2 cell differentiation and treat allergic rhinitis (AR).

Methods: Established AR model mice by ovalbumin (OVA) and isolated the peripheral blood monocytes (PBMCs), evaluating behavioral changes of AR mice. Analysis of histopathological characteristics by HE. sIgE, IL-4, and IFN-γ were detected by ELISA. RT-qPCR and Western blot detected the expression of GATA3, T-bet, and RUNX1. Using immunofluorescence to detect the expression of GATA and T-bet.

Results: Knockout GATA3 suppressed the expression of GATA3 and concentration of sIgE and IL-4, and promoted the expression of T-bet and concentration of IFN-γ. Knockout GATA3 alleviates inflammation in AR mice by increasing the CD4+ IFN-γ+ cell rate and decreasing the CD4+ IL-4+ cell rate. RUNX1 and GATA3 were both expressed in the nucleus, GATA3 could bind and interact with RUNX1, si-RUNX1 reversed the effect of sh-GATA3, RUNX1 regulated the balance of Th1/Th2 to alleviate inflammation in AR mice by down-regulating expression of GATA3.

Conclusion: GATA3 regulated the balance of Th1/Th2 cells maybe by the interaction between RUNX1 to improve anti-allergic and anti-inflammatory potential strategies in AR therapy.

Keywords: Allergic rhinitis (AR); GATA3; Th1/Th2 cell differentiation; inflammation; runt-related transcription factor 1(RUNX1).

Plain language summary

This study examined the role of GATA3 and RUNX1 in allergic rhinitis (AR). The results showed that in AR mice, the expression of GATA3 increases, and inhibiting GATA3 can promote Th1 activation and alleviate the inflammatory response. In addition, GATA3 regulates the balance of Th1/Th2 cells by inhibiting RUNX1. These discoveries suggest that the way GATA3/RUNX1 axis works might be key in causing AR.

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Conflict of interest statement

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

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Graphical abstract
Figure 1.
Figure 1.
GATA3 regulated the balance of Th1/Th2 in peripheral blood mononuclear cells (PBMCs) of AR mice. (A) Measured scoring standards for each group of mice. (B) Detected concentration of sIgE by ELISA. (C) The mucosal tissue of the nasal cavity by HE (Scale bar = 20 μm). (D) Detected the expression of GATA3 and T-bet by RT-qPCR. (E) Detected the protein expression of GATA3 and T-bet by Western blot. (F) ELISA detection of the secretion concentration of IL-4 and IFN-γ. ***p < 0.001, compared with Control or NC group, #p < 0.05, ###p < 0.001, compared with AR group.
Figure 2.
Figure 2.
Knockout GATA3 could alleviate the inflammation in AR mice by regulating the balance of Th1/Th2. (A) Detected the expression of GATA3 and T-bet by RT-qPCR. (B) Detected the protein expression of GATA3 and T-bet by Western blot. (C) ELISA detection of the secretion concentration of sIgE, IL-4, and IFN-γ. (D) Analyze the percentage of CD4 + IL-4+ and CD4+ IFNγ+ T cells by Flow cytometry. (E): The mucosal tissue of the nasal cavity by HE (Scale bar = 20 μm). (F): Detected the fluorescence intensity of GATA3 and T-bet by Immunofluorescence (Scale bar = 20 μm). (G) Detected the expression of GATA3 and T-bet by RT-qPCR. (H) Detected the protein expression of GATA3 and T-bet by Western blot. *p < 0.05, ***p < 0.001, compared with Control group, ###p < 0.001, compared with AR group.
Figure 3.
Figure 3.
Interaction between RUNX1 and GATA3. (A) Target protein prediction of GATA3 by STRING database. (B) Verifies the relationship between GATA3 and RUNX1 by CO-IP. (C) Detected the protein enrichment by CHIP-qPCR. D: The fluorescence co-localization experiment (Scale bar = 20 μm). ***p < 0.001, compared with the sh-NC group.
Figure 4.
Figure 4.
GATA3 regulated the balance of Th1/Th2 in PBMCs of AR mice by interaction between RUNX1. (A) Detected the transfection efficiency by RT-qPCR. (B) Detected the expression of RUNX1, GATA3 and T-bet by RT-qPCR. (C) ELISA detection of the secretion concentration of IL-4 and IFN-γ. (D) Detected the protein expression of RUNX1, GATA3 and T-bet by Western blot. ***p < 0.001, compared with AR group, #p < 0.05, ##p < 0.01, compared with AR+sh-GATA3 group.
Figure 5.
Figure 5.
RUNX1 alleviated the inflammation in AR mice by interaction between GATA3 to regulate the balance of Th1/Th2. (A) Detected the expression of RUNX1, GATA3 and T-bet by RT-qPCR. (B) ELISA detection of the secretion concentration of sIgE, IL-4, and IFN-γ. (C) Detected the protein expression of RUNX1, GATA3 and T-bet by Western blot. (D) Analyze the percentage of CD4+IL-4+ and CD4+ IFNγ+ T cells by Flow cytometry. (E) The mucosal tissue of the nasal cavity by HE (Scale bar = 20 μm). (F) Detected the fluorescence intensity of GATA3 and T-bet by Immunofluorescence (Scale bar = 20 μm). (G) Detected the expression of RUNX1, GATA3 and T-bet by RT-qPCR. *p < 0.05, **p < 0.01, ***p < 0.001, compared with AR group.
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