Interleukin-19 impairment in active Crohn's disease patients.

The exact function of interleukin-19 (IL-19) on immune response is poorly understood. In mice, IL-19 up-regulates TNFα and IL-6 expression and its deficiency increases susceptibility to DSS-induced colitis. In humans, IL-19 favors a Th2 response and is elevated in several diseases. We here investiga...

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Autores principales:	Elisabet Cantó, Esther Garcia Planella, Carlos Zamora-Atenza, Juan Camilo Nieto, Jordi Gordillo, Ma Angels Ortiz, Isidoro Metón, Elena Serrano, Esteban Vegas, Orlando García-Bosch, Cándido Juárez, Sílvia Vidal
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/385015253f4f4b73a045699f04ad175c
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spelling	oai:doaj.org-article:385015253f4f4b73a045699f04ad175c2021-11-18T08:24:08ZInterleukin-19 impairment in active Crohn's disease patients.1932-620310.1371/journal.pone.0093910https://doaj.org/article/385015253f4f4b73a045699f04ad175c2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24718601/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The exact function of interleukin-19 (IL-19) on immune response is poorly understood. In mice, IL-19 up-regulates TNFα and IL-6 expression and its deficiency increases susceptibility to DSS-induced colitis. In humans, IL-19 favors a Th2 response and is elevated in several diseases. We here investigate the expression and effects of IL-19 on cells from active Crohn's disease (CD) patient. Twenty-three active CD patients and 20 healthy controls (HC) were included. mRNA and protein IL-19 levels were analyzed in monocytes. IL-19 effects were determined in vitro on the T cell phenotype and in the production of cytokines by immune cells. We observed that unstimulated and TLR-activated monocytes expressed significantly lower IL-19 mRNA in active CD patients than in HC (logFC = -1.97 unstimulated; -1.88 with Pam3CSK4; and -1.91 with FSL-1; p<0.001). These results were confirmed at protein level. Exogenous IL-19 had an anti-inflammatory effect on HC but not on CD patients. IL-19 decreased TNFα production in PBMC (850.7 ± 75.29 pg/ml vs 2626.0 ± 350 pg/ml; p<0.01) and increased CTLA4 expression (22.04 ± 1.55% vs 13.98 ± 2.05%; p<0.05) and IL-4 production (32.5 ± 8.9 pg/ml vs 13.5 ± 2.9 pg/ml; p<0.05) in T cells from HC. IL-10 regulated IL-19 production in both active CD patients and HC. We observed that three of the miRNAs that can modulate IL-19 mRNA expression, were up-regulated in monocytes from active CD patients. These results suggested that IL-19 had an anti-inflammatory role in this study. Defects in IL-19 expression and the lack of response to this cytokine could contribute to inflammatory mechanisms in active CD patients.Elisabet CantóEsther Garcia PlanellaCarlos Zamora-AtenzaJuan Camilo NietoJordi GordilloMa Angels OrtizIsidoro MetónElena SerranoEsteban VegasOrlando García-BoschCándido JuárezSílvia VidalPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e93910 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elisabet Cantó Esther Garcia Planella Carlos Zamora-Atenza Juan Camilo Nieto Jordi Gordillo Ma Angels Ortiz Isidoro Metón Elena Serrano Esteban Vegas Orlando García-Bosch Cándido Juárez Sílvia Vidal Interleukin-19 impairment in active Crohn's disease patients.
description	The exact function of interleukin-19 (IL-19) on immune response is poorly understood. In mice, IL-19 up-regulates TNFα and IL-6 expression and its deficiency increases susceptibility to DSS-induced colitis. In humans, IL-19 favors a Th2 response and is elevated in several diseases. We here investigate the expression and effects of IL-19 on cells from active Crohn's disease (CD) patient. Twenty-three active CD patients and 20 healthy controls (HC) were included. mRNA and protein IL-19 levels were analyzed in monocytes. IL-19 effects were determined in vitro on the T cell phenotype and in the production of cytokines by immune cells. We observed that unstimulated and TLR-activated monocytes expressed significantly lower IL-19 mRNA in active CD patients than in HC (logFC = -1.97 unstimulated; -1.88 with Pam3CSK4; and -1.91 with FSL-1; p<0.001). These results were confirmed at protein level. Exogenous IL-19 had an anti-inflammatory effect on HC but not on CD patients. IL-19 decreased TNFα production in PBMC (850.7 ± 75.29 pg/ml vs 2626.0 ± 350 pg/ml; p<0.01) and increased CTLA4 expression (22.04 ± 1.55% vs 13.98 ± 2.05%; p<0.05) and IL-4 production (32.5 ± 8.9 pg/ml vs 13.5 ± 2.9 pg/ml; p<0.05) in T cells from HC. IL-10 regulated IL-19 production in both active CD patients and HC. We observed that three of the miRNAs that can modulate IL-19 mRNA expression, were up-regulated in monocytes from active CD patients. These results suggested that IL-19 had an anti-inflammatory role in this study. Defects in IL-19 expression and the lack of response to this cytokine could contribute to inflammatory mechanisms in active CD patients.
format	article
author	Elisabet Cantó Esther Garcia Planella Carlos Zamora-Atenza Juan Camilo Nieto Jordi Gordillo Ma Angels Ortiz Isidoro Metón Elena Serrano Esteban Vegas Orlando García-Bosch Cándido Juárez Sílvia Vidal
author_facet	Elisabet Cantó Esther Garcia Planella Carlos Zamora-Atenza Juan Camilo Nieto Jordi Gordillo Ma Angels Ortiz Isidoro Metón Elena Serrano Esteban Vegas Orlando García-Bosch Cándido Juárez Sílvia Vidal
author_sort	Elisabet Cantó
title	Interleukin-19 impairment in active Crohn's disease patients.
title_short	Interleukin-19 impairment in active Crohn's disease patients.
title_full	Interleukin-19 impairment in active Crohn's disease patients.
title_fullStr	Interleukin-19 impairment in active Crohn's disease patients.
title_full_unstemmed	Interleukin-19 impairment in active Crohn's disease patients.
title_sort	interleukin-19 impairment in active crohn's disease patients.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/385015253f4f4b73a045699f04ad175c
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Interleukin-19 impairment in active Crohn's disease patients.

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