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dc.contributor.authorJijon, H B
dc.contributor.authorDiaz, O E
dc.contributor.authorDas, S
dc.contributor.authorDe Calisto, J
dc.contributor.authorPittet, M J
dc.contributor.authorMora, J R
dc.contributor.authorBelkaid, Y
dc.contributor.authorXavier, R J
dc.contributor.authorVillablanca, E J
dc.contributor.authorYaffe, Michael B
dc.contributor.authorSuarez Lopez, Lucia
dc.date.accessioned2018-07-13T18:21:57Z
dc.date.available2018-07-13T18:21:57Z
dc.date.issued2017-11
dc.date.submitted2017-03
dc.identifier.issn1933-0219
dc.identifier.issn1935-3456
dc.identifier.urihttp://hdl.handle.net/1721.1/116988
dc.description.abstractRetinoic acid (RA), a dietary vitamin A metabolite, is crucial in maintaining intestinal homeostasis. RA acts on intestinal leukocytes to modulate their lineage commitment and function. Although the role of RA has been characterized in immune cells, whether intestinal epithelial cells (IECs) rely on RA signaling to exert their immune-regulatory function has not been examined. Here we demonstrate that lack of RA receptor α (RARα) signaling in IECs results in deregulated epithelial lineage specification, leading to increased numbers of goblet cells and Paneth cells. Mechanistically, lack of RARα resulted in increased KLF4 + goblet cell precursors in the distal bowel, whereas RA treatment inhibited klf4 expression and goblet cell differentiation in zebrafish. These changes in secretory cells are associated with increased Reg3g, reduced luminal bacterial detection, and an underdeveloped intestinal immune system, as evidenced by an almost complete absence of lymphoid follicles and gut resident mononuclear phagocytes. This underdeveloped intestinal immune system shows a decreased ability to clear infection with Citrobacter rodentium. Collectively, our findings indicate that epithelial cell-intrinsic RARα signaling is critical to the global development of the intestinal immune system.en_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/MI.2017.91en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titleIntestinal epithelial cell-specific RARα depletion results in aberrant epithelial cell homeostasis and underdeveloped immune systemen_US
dc.typeArticleen_US
dc.identifier.citationJijon, H. B. et al. “Intestinal Epithelial Cell-Specific RARα Depletion Results in Aberrant Epithelial Cell Homeostasis and Underdeveloped Immune System.” Mucosal Immunology 11, 3 (November 2017): 703–715 © 2018 The Author(s)en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorYaffe, Michael B
dc.contributor.mitauthorSuarez Lopez, Lucia
dc.relation.journalMucosal Immunologyen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-07-13T14:16:43Z
dspace.orderedauthorsJijon, H B; Suarez-Lopez, L; Diaz, O E; Das, S; De Calisto, J; Yaffe, M B; Pittet, M J; Mora, J R; Belkaid, Y; Xavier, R J; Villablanca, E Jen_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-9547-3251
dc.identifier.orcidhttps://orcid.org/0000-0002-3719-0536
mit.licenseOPEN_ACCESS_POLICYen_US


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