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Interferon Regulatory Factor 6 Determines Epithelial Cell Development and Immunity

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE245972 | GEO | 2023/11/01

REPOSITORIES: GEO

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Interferon regulatory factor 6 (IRF6) determines intestinal epithelial cell development and immunity.

Project description:Intestinal epithelial cell (IEC) responses to interferon (IFN) favor antiviral defense with minimal cytotoxicity, but IEC-specific factors that regulate these responses remain poorly understood. Interferon regulatory factors (IRFs) are a family of nine related transcription factors, and IRF6 is preferentially expressed by epithelial cells, but its roles in IEC immunity are unknown. In this study, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) screens found that Irf6 deficiency enhanced IFN-stimulated antiviral responses in transformed mouse IECs but not macrophages. Furthermore, knockout (KO) of Irf6 in IEC organoids resulted in profound changes to homeostasis and immunity gene expression. Irf6 KO organoids grew more slowly, and single-cell ribonucleic acid sequencing indicated reduced expression of genes in epithelial differentiation and immunity pathways. IFN-stimulated gene expression was also significantly different in Irf6 KO organoids, with increased expression of stress and apoptosis-associated genes. Functionally, the transcriptional changes in Irf6 KO organoids were associated with increased cytotoxicity upon IFN treatment or inflammasome activation. These data indicate a previously unappreciated role for IRF6 in IEC biology, including regulation of epithelial development and moderation of innate immune responses to minimize cytotoxicity and maintain barrier function.

| S-EPMC11323225 | biostudies-literature

Interferon Regulatory Factor 6 Determines Epithelial Cell Development and Immunity 1

Project description:Intestinal epithelial cells (IECs) form a primary barrier against microbial invasion. Prior studies of enteric pathogens have indicated that IEC defense mechanisms are distinct from those of other cell types. For example, antiviral defense of IECs depends on type III interferon whereas most cell types depend on type I IFN. Interferon regulatory factors (IRFs) are a family of transcription factors with well-described roles in stimulation of IFN cytokines, but IRF6 is unique in its preferential expression by epithelial lineages. IRF6 has primarily been studied in epidermal development, but has relatively unknown roles in the intestinal epithelium. Here, we found that Irf6 KO regulated IFN-stimulated antiviral immunity of IECs but had no effect on macrophages. RNseq analysis of Irf6 KO cells showed significant differences in the IFN-stimulated gene expression program that correlated with the magnitude of antiviral gene stimulation. We also found significant baseline phenotypic and transcriptional changes in Irf6 KO IECs, with reduced rate of growth and preturbation of growth and differentiation pathway genes. Knockout of Irf6 in primary IEC organoids also resulted in slower growth and smaller size. Transcriptional analysis of Irf6 KO organoids indicated reduced expression of genes in the epithelial differentiation pathwya, including Wnt and Notch pathway genes, as well as increased expression of a subset of IFN-stimulated genes. These data indicate a previously unappreciated role of Irf6 in shaping the IEC transcriptome, including baseline epithelial development genes and IFN-stimulated genes.

2023-11-01 | GSE245970 | GEO

Interferon Regulatory Factor 6 Determines Epithelial Cell Development and Immunity 2

2023-11-01 | GSE245971 | GEO

Interferon Regulatory Factor 6 Determines Epithelial Cell Development and Immunity

Project description:Interferon Regulatory Factor 6 Determines Epithelial Cell Development and Immunity

| PRJNA1030897 | ENA

Interferon Regulatory Factor 6 Determines Epithelial Cell Development and Immunity 1

Project description:Interferon Regulatory Factor 6 Determines Epithelial Cell Development and Immunity 1

| PRJNA1030898 | ENA

Interferon Regulatory Factor 6 Determines Epithelial Cell Development and Immunity 2

Project description:Interferon Regulatory Factor 6 Determines Epithelial Cell Development and Immunity 2

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Predisposal of Interferon Regulatory Factor 1 Deficiency to Accumulate DNA Damage and Promote Osteoarthritis Development in Cartilage

Project description:This SuperSeries is composed of the SubSeries listed below.

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Conversion of MyoD to a neurogenic factor: binding site specificity determines lineage

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-07-31 | E-GEOD-64627 | biostudies-arrayexpress

Transcription factor TCF1 binds Rorgt and orchestrates a regulatory network that determines homeostatic Th17 cell state

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-11-03 | GSE233908 | GEO

Transcription factor trapping by RNA in gene regulatory elements

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-10-29 | E-GEOD-68198 | biostudies-arrayexpress

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