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

doi:10.1016/j.bbrc.2022.11.095

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 journal › Article › peer-review

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 language	English
Pages (from-to)	32-39
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	640
DOIs	https://doi.org/10.1016/j.bbrc.2022.11.095
Publication status	Published - 2023 Jan 15

Bibliographical note

Funding Information:
This work was supported by a grant from the Global Research Laboratory (GRL) Program of the National Research Foundation of Korea [NRF- 2016K1A1A2912755 ]; and the Brain Korea 21 (BK21) PLUS program, J.-H. Kim is a fellowship awardee by the BK21 PLUS program Republic of Korea.

Publisher Copyright:
© 2022 The Authors

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2022.11.095

Cite this

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title = "Intranasal administration of nucleus-deliverable GATA3-TMD alleviates the symptoms of allergic asthma",

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.",

author = "Lee, {Su Hyeon} and Kim, {Jung Ho} and Yekyung Seong and Moon, {Jae Seung} and Yuna Kim and Shin, {Bo Young} and Shin, {Jin Su} and Jiyoon Park and Park, {Choon Sik} and Lee, {Sang Kyou}",

note = "Funding Information: This work was supported by a grant from the Global Research Laboratory (GRL) Program of the National Research Foundation of Korea [NRF- 2016K1A1A2912755 ]; and the Brain Korea 21 (BK21) PLUS program, J.-H. Kim is a fellowship awardee by the BK21 PLUS program Republic of Korea. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2023",

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doi = "10.1016/j.bbrc.2022.11.095",

language = "English",

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AU - Lee, Su Hyeon

AU - Kim, Jung Ho

AU - Seong, Yekyung

AU - Moon, Jae Seung

AU - Kim, Yuna

AU - Shin, Bo Young

AU - Shin, Jin Su

AU - Park, Jiyoon

AU - Park, Choon Sik

AU - Lee, Sang Kyou

N1 - Funding Information: This work was supported by a grant from the Global Research Laboratory (GRL) Program of the National Research Foundation of Korea [NRF- 2016K1A1A2912755 ]; and the Brain Korea 21 (BK21) PLUS program, J.-H. Kim is a fellowship awardee by the BK21 PLUS program Republic of Korea. Publisher Copyright: © 2022 The Authors

PY - 2023/1/15

Y1 - 2023/1/15

N2 - 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.

AB - 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.

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SN - 0006-291X

VL - 640

SP - 32

EP - 39

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

ER -

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

Abstract

Bibliographical note

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UN SDGs

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