GATA-3 and Its Association with Allergic Diseases and Immune Regulation: A Systematic Review

Background/Objectives: GATA-binding protein 3 (GATA-3) is a crucial transcription factor that drives type 2 immune responses, and it is actively involved in allergic conditions such as asthma, allergic rhinitis (AR), and atopic dermatitis (AD). However, the molecular mechanisms GATA-3 uses to modulate immune responses and its potential therapeutic targeting are not fully understood. This systematic review aimed to summarize studies on the role of GATA-3 in immune responses, particularly in allergic diseases, and evaluate GATA-3’s potential as a therapeutic target. Methods: We searched PubMed, Scopus, Web of Science, Cochrane, and Science Direct for studies published before April 2025. Articles were sifted through using predefined criteria, and risk of bias was measured with RoB 2 for clinical trials and SYRCLE for animal models and in vitro studies; evidence was graded using the GRADE system. Results: Twenty-nine eligible studies reported that GATA-3 is a key regulator of Th2 and ILC2 differentiation, promoting the production of IL-4, IL-5, and IL-13. Animal models and in vitro studies demonstrated its role in exacerbating allergic inflammation and highlighted the promise of targeting strategies such as DNAzymes and nanocapsules. Clinical trials showed that targeting GATA-3, particularly with DNAzymes, can reduce allergic responses in asthma. Conclusions: GATA-3’s role in driving allergic inflammation through Th2 and ILC2 pathways suggests it as a promising therapeutic target. Understanding its broader regulatory mechanisms is imperative for designing effective GATA-3 targeting-based therapies.