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Suppression of Allergic Asthma by Loss of Function of Miz1-mediated Th1 Skewing.

ABSTRACT: Asthma is the most prevalent chronic respiratory disease worldwide. There is currently no cure, and it remains an important cause of morbidity and mortality. Here we report that lung-specific loss of function of the transcription factor Miz1 (c-Myc-interacting zinc finger protein-1) upregulates the pro-T-helper cell type 1 cytokine IL-12. Upregulation of IL-12 in turn stimulates a Th1 response, thereby counteracting T-helper cell type 2 response and preventing the allergic response in mouse models of house dust mite- and OVA (ovalbumin)-induced asthma. Using transgenic mice expressing Cre under a cell-specific promoter, we demonstrate that Miz1 acts in lung epithelial cells and dendritic cells in asthma. Chromatin immunoprecipitation coupled with high-throughput DNA sequencing or quantitative PCR reveals the binding of Miz1 on the Il12 promoter indicating direct repression of IL-12 by Miz1. In addition, HDAC1 (histone deacetylase 1) is recruited to the Il12 promoter in a Miz1-depdenent manner, suggesting epigenetic repression of Il12 by Miz1. Furthermore, Miz1 is upregulated in the lungs of asthmatic mice. Our data together suggest that Miz1 is upregulated during asthma, which in turn promotes asthma pathogenesis by preventing Th1 skewing through the transcriptional repression of IL-12.

SUBMITTER: Do-Umehara HC

PROVIDER: S-EPMC9447135 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Suppression of Allergic Asthma by Loss of Function of Miz1-mediated Th1 Skewing.

Do-Umehara Hanh Chi HC Chen Cong C Zhang Qiao Q Schleimer Robert P RP Budinger G R Scott GRS Liu Jing J

American journal of respiratory cell and molecular biology 20220901 3

Asthma is the most prevalent chronic respiratory disease worldwide. There is currently no cure, and it remains an important cause of morbidity and mortality. Here we report that lung-specific loss of function of the transcription factor Miz1 (c-Myc-interacting zinc finger protein-1) upregulates the pro-T-helper cell type 1 cytokine IL-12. Upregulation of IL-12 in turn stimulates a Th1 response, thereby counteracting T-helper cell type 2 response and preventing the allergic response in mouse mode ...[more]

PMID: 35833903

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Suppression of Allergic Asthma by Loss of Function of Miz1-mediated Th1 Skewing.

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Suppression of Allergic Asthma by Loss of Function of Miz1-mediated Th1 Skewing.

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