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 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.
Department of Immunology Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Elisabet
E
Cantó
Department of Digestive Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Esther
E
Garcia Planella
Department of Immunology Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Carlos
C
Zamora-Atenza
Department of Immunology Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Juan Camilo
JC
Nieto
Department of Digestive Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Jordi
J
Gordillo
Department of Immunology Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Ma Angels
MA
Ortiz
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
Isidoro
I
Metón
Bioinformatics Platform, PSCT Platforms, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Elena
E
Serrano
Department of Statistical, Faculty of Biology, University of Barcelona, Barcelona, Spain.
Esteban
E
Vegas
Department of Digestive, Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Barcelona, Spain.
Orlando
O
García-Bosch
Department of Immunology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain.
Cándido
C
Juárez
Department of Immunology Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Universitat Autònoma de Barcelona, Barcelona, Spain.
Sílvia
S
Vidal
D000328:Adult; D000368:Aged; D060908:CTLA-4 Antigen / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology; D007378:Interleukins / Q000096:biosynthesis / Q000097:blood / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C508609:IL10 protein, human; C421250:IL19 protein, human; D007378:Interleukins; D035683:MicroRNAs; D011994:Recombinant Proteins; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10