Intestinal epithelial cell autophagy is required to protect against TNF-induced apoptosis during chronic colitis in mice
Genome-wide association studies have linked polymorphisms in the autophagy gene ATG16L1 with susceptibility to inflammatory bowel disease (IBD). However, the cell-type-specific effects of autophagy on the regulation of chronic intestinal inflammation have not been investigated. Here, we assessed the...
| मुख्य लेखकों: | , , |
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| स्वरूप: | Journal article |
| भाषा: | English |
| प्रकाशित: |
Cell Press
2018
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| _version_ | 1826280124973056000 |
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| author | Pott, J Kabat, A Maloy, K |
| author_facet | Pott, J Kabat, A Maloy, K |
| author_sort | Pott, J |
| collection | OXFORD |
| description | Genome-wide association studies have linked polymorphisms in the autophagy gene ATG16L1 with susceptibility to inflammatory bowel disease (IBD). However, the cell-type-specific effects of autophagy on the regulation of chronic intestinal inflammation have not been investigated. Here, we assessed the effect of myeloid-specific or intestinal epithelial cell (IEC)-specific deletion of Atg16l1 on chronic colitis triggered by the intestinal opportunistic pathogen Helicobacter hepaticus in mice. Although Atg16l1 deficiency in myeloid cells had little effect on disease, mice selectively lacking Atg16l1 in IECs (Atg16l1VC) developed severely exacerbated pathology, accompanied by elevated pro-inflammatory cytokine secretion and increased IEC apoptosis. Using ex vivo IEC organoids, we demonstrate that autophagy intrinsically controls TNF-induced apoptosis and in vivo blockade of TNF attenuated the exacerbated pathology in Atg16l1VC mice. These findings suggest that the IBD susceptibility gene ATG16L1 and the process of autophagy within the epithelium control inflammation-induced apoptosis and barrier integrity to limit chronic intestinal inflammation |
| first_indexed | 2024-03-07T00:09:01Z |
| format | Journal article |
| id | oxford-uuid:7891b027-53b5-4b13-aa20-5d6fb5a5d3b2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:09:01Z |
| publishDate | 2018 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:7891b027-53b5-4b13-aa20-5d6fb5a5d3b22022-03-26T20:31:31ZIntestinal epithelial cell autophagy is required to protect against TNF-induced apoptosis during chronic colitis in miceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7891b027-53b5-4b13-aa20-5d6fb5a5d3b2EnglishSymplectic Elements at OxfordCell Press2018Pott, JKabat, AMaloy, KGenome-wide association studies have linked polymorphisms in the autophagy gene ATG16L1 with susceptibility to inflammatory bowel disease (IBD). However, the cell-type-specific effects of autophagy on the regulation of chronic intestinal inflammation have not been investigated. Here, we assessed the effect of myeloid-specific or intestinal epithelial cell (IEC)-specific deletion of Atg16l1 on chronic colitis triggered by the intestinal opportunistic pathogen Helicobacter hepaticus in mice. Although Atg16l1 deficiency in myeloid cells had little effect on disease, mice selectively lacking Atg16l1 in IECs (Atg16l1VC) developed severely exacerbated pathology, accompanied by elevated pro-inflammatory cytokine secretion and increased IEC apoptosis. Using ex vivo IEC organoids, we demonstrate that autophagy intrinsically controls TNF-induced apoptosis and in vivo blockade of TNF attenuated the exacerbated pathology in Atg16l1VC mice. These findings suggest that the IBD susceptibility gene ATG16L1 and the process of autophagy within the epithelium control inflammation-induced apoptosis and barrier integrity to limit chronic intestinal inflammation |
| spellingShingle | Pott, J Kabat, A Maloy, K Intestinal epithelial cell autophagy is required to protect against TNF-induced apoptosis during chronic colitis in mice |
| title | Intestinal epithelial cell autophagy is required to protect against TNF-induced apoptosis during chronic colitis in mice |
| title_full | Intestinal epithelial cell autophagy is required to protect against TNF-induced apoptosis during chronic colitis in mice |
| title_fullStr | Intestinal epithelial cell autophagy is required to protect against TNF-induced apoptosis during chronic colitis in mice |
| title_full_unstemmed | Intestinal epithelial cell autophagy is required to protect against TNF-induced apoptosis during chronic colitis in mice |
| title_short | Intestinal epithelial cell autophagy is required to protect against TNF-induced apoptosis during chronic colitis in mice |
| title_sort | intestinal epithelial cell autophagy is required to protect against tnf induced apoptosis during chronic colitis in mice |
| work_keys_str_mv | AT pottj intestinalepithelialcellautophagyisrequiredtoprotectagainsttnfinducedapoptosisduringchroniccolitisinmice AT kabata intestinalepithelialcellautophagyisrequiredtoprotectagainsttnfinducedapoptosisduringchroniccolitisinmice AT maloyk intestinalepithelialcellautophagyisrequiredtoprotectagainsttnfinducedapoptosisduringchroniccolitisinmice |