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KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972715/ https://www.ncbi.nlm.nih.gov/pubmed/26838049 http://dx.doi.org/10.1038/mi.2016.1 |
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author | Goodman, Wendy A. Omenetti, Sara Date, Dipali Di Martino, Luca De Salvo, Carlo Kim, Gun-Dong Chowdhry, Saleem Bamias, Giorgos Cominelli, Fabio Pizarro, Theresa T. Mahabeleshwar, Ganapati H. |
author_facet | Goodman, Wendy A. Omenetti, Sara Date, Dipali Di Martino, Luca De Salvo, Carlo Kim, Gun-Dong Chowdhry, Saleem Bamias, Giorgos Cominelli, Fabio Pizarro, Theresa T. Mahabeleshwar, Ganapati H. |
author_sort | Goodman, Wendy A. |
collection | PubMed |
description | 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 NFκB signaling, while simultaneously suppressing anti-inflammatory gene expression through repression of 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 against chemically-induced colitis; this highlights the central role of myeloid KLF6 in promoting intestinal inflammation. Collectively, our results point to a novel gene regulatory program underlying pathogenic, pro-inflammatory macrophage activation in the setting of chronic intestinal inflammation. |
format | Online Article Text |
id | pubmed-4972715 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-49727152016-08-22 KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation Goodman, Wendy A. Omenetti, Sara Date, Dipali Di Martino, Luca De Salvo, Carlo Kim, Gun-Dong Chowdhry, Saleem Bamias, Giorgos Cominelli, Fabio Pizarro, Theresa T. Mahabeleshwar, Ganapati H. Mucosal Immunol Article 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 NFκB signaling, while simultaneously suppressing anti-inflammatory gene expression through repression of 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 against chemically-induced colitis; this highlights the central role of myeloid KLF6 in promoting intestinal inflammation. Collectively, our results point to a novel gene regulatory program underlying pathogenic, pro-inflammatory macrophage activation in the setting of chronic intestinal inflammation. 2016-02-03 2016-09 /pmc/articles/PMC4972715/ /pubmed/26838049 http://dx.doi.org/10.1038/mi.2016.1 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Goodman, Wendy A. Omenetti, Sara Date, Dipali Di Martino, Luca De Salvo, Carlo Kim, Gun-Dong Chowdhry, Saleem Bamias, Giorgos Cominelli, Fabio Pizarro, Theresa T. Mahabeleshwar, Ganapati H. KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation |
title | KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation |
title_full | KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation |
title_fullStr | KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation |
title_full_unstemmed | KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation |
title_short | KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation |
title_sort | klf6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972715/ https://www.ncbi.nlm.nih.gov/pubmed/26838049 http://dx.doi.org/10.1038/mi.2016.1 |
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