Intranasal administration of nucleus-deliverable GATA3-TMD alleviates the symptoms of allergic asthma

Su Hyeon Lee, Jung Ho Kim, Yekyung Seong, Jae Seung Moon, Yuna Kim, Bo Young Shin, Jin Su Shin, Jiyoon Park, Choon Sik Park, Sang Kyou Lee

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Although the T helper 2 (Th2) subset is a critical player in the humoral immune response to extracellular parasites and suppression of Th1-mediated inflammation, Th2 cells have been implicated in allergic inflammatory diseases such as asthma, allergic rhinitis, and atopic dermatitis. GATA binding protein 3 (GATA3) is a primary transcription factor that mediates Th2 differentiation and secretion of Th2 cytokines, including IL-4, IL-5, and IL-13. Here, a nucleus-deliverable form of GATA3-transcription modulation domain (TMD) (ndG3-TMD) was generated using Hph-1 human protein transduction domain (PTD) to modulate the transcriptional function of endogenous GATA3 without genetic manipulation. ndG3-TMD was shown to be efficiently delivered into the cell nucleus quickly without affecting cell viability or intracellular signaling events for T cell activation. ndG3-TMD exhibited a specific inhibitory function for the endogenous GATA3-mediated transcription, such as Th2 cell differentiation and Th2-type cytokine production. Intranasal administration of ndG3-TMD significantly alleviated airway hyperresponsiveness, infiltration of immune cells, and serum IgE level in an OVA-induced mouse model of asthma. Also, Th2 cytokine secretion by the splenocytes isolated from the ndG3-TMD-treated mice substantially decreased. Our results suggest that ndG3-TMD can be a new therapeutic reagent to suppress Th2-mediated allergic diseases through intranasal delivery.

Original languageEnglish
Pages (from-to)32-39
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume640
DOIs
Publication statusPublished - 2023 Jan 15

Bibliographical note

Publisher Copyright:
© 2022 The Authors

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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