Interleukin-19 impairment in active Crohn's disease patients

PLoS One. 2014 Apr 9;9(4):e93910. doi: 10.1371/journal.pone.0093910. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CTLA-4 Antigen / biosynthesis
  • CTLA-4 Antigen / genetics
  • Cells, Cultured
  • Crohn Disease / immunology
  • Crohn Disease / metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Interleukin-10 / physiology
  • Interleukins / biosynthesis
  • Interleukins / blood
  • Interleukins / deficiency*
  • Interleukins / genetics
  • Interleukins / pharmacology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / drug effects
  • Male
  • MicroRNAs / genetics
  • Middle Aged
  • Monocytes / metabolism*
  • Recombinant Proteins / pharmacology
  • Th2 Cells / immunology
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / physiology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CTLA-4 Antigen
  • CTLA4 protein, human
  • IL10 protein, human
  • IL19 protein, human
  • Interleukins
  • MicroRNAs
  • Recombinant Proteins
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • Interleukin-10

Grants and funding

Ministerio de Economia i competitividad PS09/132 Instituto de Salud Carlos III. Sílvia Vidal was supported by “Fondo Investigaciones Sanitarias” and participant in the Program for Stabilization of Investigators of the “Direcció d’Estrategia i Coordinació del Departament Salut de la Generalitat de Catalunya”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.