Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Enfermedades Inflamatorias del Intestino/terapia , Modelos Educacionales , Educación del Paciente como Asunto , Adulto , Anciano , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Calidad de Vida , Sociedades Médicas , Encuestas y Cuestionarios , Adulto JovenRESUMEN
We analyzed interleukin (IL) 12 and IL-23 production by monocyte-derived dendritic cells (mono-DCs). Mycobacterium tuberculosis H37Rv and zymosan preferentially induced IL-23. IL-23 but not IL-12 was efficiently induced by the combination of nucleotide-binding oligodimerization domain and Toll-like receptor (TLR) 2 ligands, which mimics activation by M. tuberculosis, or by the human dectin-1 ligand beta-glucan alone or in combination with TLR2 ligands, mimicking induction by zymosan. TLR2 ligands inhibited IL-12 and increased IL-23 production. DC priming with interferon (IFN) gamma strongly increased IL-12 production, but was not required for IL-23 production and inhibited IL-23 production induced by beta-glucan. The pattern of IL-12 and IL-23 induction was reflected in accumulation of the IL-12p35 and IL-23p19 transcripts, respectively, but not IL-12/23p40. Although IL-23, transforming growth factor beta, and IL-6 contained in the supernatants of activated mono-DCs played a role in the induction of IL-17 by human CD4(+) T cells, IL-1beta, in combination with one or more of those factors, was required for IL-17 production, and its production determined the differential ability of the stimuli used to elicit mono-DCs to produce soluble factors directing IL-17 production. Thus, the differential ability of pathogens to induce antigen-presenting cells to produce cytokines regulates the immune response to infection.
Asunto(s)
Células Dendríticas/inmunología , Regulación de la Expresión Génica , Interleucina-12/genética , Interleucina-23/genética , Células Dendríticas/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interferón gamma/farmacología , Metionina/metabolismo , Mycobacterium tuberculosis/inmunología , Receptor Toll-Like 2/inmunología , Receptor Toll-Like 2/fisiología , Zimosan/farmacologíaRESUMEN
CARD15 on chromosome 16 is the only IBD susceptibility gene identified among several mapped loci. Its recurrent variants R702W, G908R and L1007fs have shown significant association with Crohn's disease (CD), but not with ulcerative colitis (UC), in different Caucasian populations. We analysed these three variants in 184 CD and 92 UC Italian patients and in 177 healthy controls. L1007fs and G908R were independently associated with CD, while R702W showed a nonsignificant increase. After combining the three variants together, 32.6% of CD patients were positive vs 18.6% of the controls. The association was stronger for homozygotes and compound heterozygotes, OR 13.9 (1.8-108), and weaker but still significant for simple heterozygotes, OR 1.7 (1.0-2.9). An excess of homozygotes/compound heterozygotes also resulted from the comparison with Hardy-Weinberg expectations. Phenotype-genotype correlations were analysed first by univariate logistic regression and then by multivariate analysis, the effect of CARD15 positivity being adjusted according to the status of smoking, familiarity and sex, so as to focus on the predictivity of genetic and environmental risk factors on the clinical phenotype. Significant risk estimates of the CARD15 genotype were obtained for stricturing vs inflammatory behaviour, OR 2.76 (1.2-6.3), and for penetrating behaviour, 2.59 (1.0-6.6), and marginally significant for ileal vs colic location, OR 3.0 (0.9-9.8). Our findings indicate that the association of the CARD15 genotype with behaviour and location of disease holds also for the Italian population.