KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation.

Mucosal Immunology
W A GoodmanGanapati H Mahabeleshwar

Abstract

Inflammatory bowel disease (IBD) is associated with dysregulated macrophage responses, such that quiescent macrophages acquire a pro-inflammatory activation state and contribute to chronic intestinal inflammation. The transcriptional events governing macrophage activation and gene expression in the context of chronic inflammation such as IBD remain incompletely understood. Here, we identify Kruppel-like transcription factor-6 (KLF6) as a critical regulator of pathogenic myeloid cell activation in human and experimental IBD. We found that KLF6 was significantly upregulated in myeloid cells and intestinal tissue from IBD patients and experimental models of IBD, particularly in actively inflamed regions of the colon. Using complementary gain- and loss-of-function studies, we observed that KLF6 promotes pro-inflammatory gene expression through enhancement of nuclear factor κB (NFκB) signaling, while simultaneously suppressing anti-inflammatory gene expression through repression of signal transducer and activator of transcription 3 (STAT3) signaling. To study the in vivo role of myeloid KLF6, we treated myeloid-specific KLF6-knockout mice (Mac-KLF6-KO) with dextran sulfate sodium (DSS) and found that Mac-KLF6-KO mice were protected ...Continue Reading

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Citations

Jul 3, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gun-Dong KimGanapati H Mahabeleshwar
Sep 14, 2017·Current Opinion in Gastroenterology·Giorgos BamiasFabio Cominelli
Jan 24, 2020·Environmental Science and Pollution Research International·Syed Waqas Ali ShahXiaohua Teng
Jun 13, 2018·Frontiers in Immunology·Heng LiGuo-Jun Zhao
Aug 20, 2016·The Journal of Biological Chemistry·Gun-Dong KimGanapati H Mahabeleshwar
Oct 2, 2020·Biomolecules·Saiful E SyafruddinTeck Yew Low
Sep 6, 2018·Nucleic Acids Research·Sebastian Carrasco ProJuan Ignacio Fuxman Bass
Jan 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gun-Dong KimGanapati H Mahabeleshwar

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Methods Mentioned

BETA
biopsies
biopsy
surgical resection
ChIP
genotyping
lavage
transfection
immunoprecipitation
immunoprecipitations
PCR

Software Mentioned

Axiovision

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