| dc.contributor.author | De Calisto, J. [Univ Mayor, Dent Sch, Ctr Genom & Bioinformat, Fac Sci, Santiago, Chile] | es_CL |
| dc.contributor.author | Jijon, H. B. | es_CL |
| dc.contributor.author | Suárez-López, L. | es_CL |
| dc.contributor.author | Díaz, O. E. | es_CL |
| dc.contributor.author | Das, S. | es_CL |
| dc.contributor.author | Yaffe, M. B. | es_CL |
| dc.contributor.author | Pittet, M. J. | es_CL |
| dc.contributor.author | Mora, J. R. | es_CL |
| dc.contributor.author | Belkaid, Y. | es_CL |
| dc.contributor.author | Xavier, R. J. | es_CL |
| dc.contributor.author | Villablanca, E. J. | es_CL |
| dc.date.accessioned | 2020-04-08T14:11:55Z | |
| dc.date.accessioned | 2020-04-13T18:12:36Z | |
| dc.date.available | 2020-04-08T14:11:55Z | |
| dc.date.available | 2020-04-13T18:12:36Z | |
| dc.date.issued | 2018 | es_CL |
| dc.identifier.citation | Jijon, H. B., Suarez-Lopez, L., Diaz, O. E., Das, S., De Calisto, J., Parada-Kusz, M., ... & Xavier, R. J. (2018). Intestinal epithelial cell-specific RARα depletion results in aberrant epithelial cell homeostasis and underdeveloped immune system. Mucosal immunology, 11(3), 703-715. | es_CL |
| dc.identifier.issn | 1933-0219 | es_CL |
| dc.identifier.issn | 1935-3456 | es_CL |
| dc.identifier.uri | https://doi.org/10.1038/mi.2017.91 | es_CL |
| dc.identifier.uri | http://repositorio.umayor.cl/xmlui/handle/sibum/6115 | |
| dc.description.abstract | Retinoic 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 alpha(RAR alpha) signaling in IECs results in deregulated epithelial lineage specification, leading to increased numbers of goblet cells and Paneth cells. Mechanistically, lack of RAR alpha 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 RARa signaling is critical to the global development of the intestinal immune system. | es_CL |
| dc.description.sponsorship | Alberta Innovates-Health Solutions Fellowship [201100215]; Samana Cay MGH Research Scholar Fund [R01-AI084880]; Helmsley Trust; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DK097485, DK062432, DK086502]; Swedish Research Council VR grant [K2015-68X-22765-01-6]; Wallenberg Academy Fellow (WAF) program | es_CL |
| dc.description.sponsorship | We thank Natalia Nedelsky for editorial assistance and members of the Villablanca lab for helpful comments. This work was supported in part by an Alberta Innovates-Health Solutions Fellowship, 201100215 to H.B.J., the Samana Cay MGH Research Scholar Fund and R01-AI084880 to M.J.P., the Helmsley Trust and NIH grants DK097485, DK062432, and DK086502 to R.J.X., and funding from Swedish Research Council VR grant K2015-68X-22765-01-6 and Wallenberg Academy Fellow (WAF) program to E.J.V. | es_CL |
| dc.language.iso | en | es_CL |
| dc.publisher | NATURE PUBLISHING GROUP | es_CL |
| dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Chile | |
| dc.source | Mucosal Immunol., MAY 2018. 11(3): p. 703-715 | |
| dc.subject | Immunology | es_CL |
| dc.title | Intestinal epithelial cell-specific RAR alpha depletion results in aberrant epithelial cell homeostasis and underdeveloped immune system | es_CL |
| dc.type | Artículo | es_CL |
| umayor.facultad | CIENCIAS | es_CL |
| umayor.politicas.sherpa/romeo | Green Accepted, Bronze, Green Published | es_CL |
| umayor.indexado | WOS:000433899600011 | es_CL |
| umayor.indexado | PMID: 29139475 | es_CL |
| dc.identifier.doi | DOI: 10.1038/mi.2017.91 | es_CL] |
| umayor.indicadores.wos-(cuartil) | Q1 | es_CL |
| umayor.indicadores.scopus-(scimago-sjr) | SCIMAGO/ INDICE H: 82 H | es_CL |