Functional Polymorphisms in the Regulatory Regions of the VNN1 Gene Are Associated with Susceptibility to Inflammatory Bowel Diseases

Gensollen, Thomas; Bourges, Christophe; Rihet, Pascal; Rostan, Agathe; Millet, Virginie; Noguchi, Tetsuro; Bourdon, Violene; Sobol, Hagay; Dubuquoy, Laurent; Bertin, Benjamin; Fuméry, Mathurin; Desreumaux, Pierre; Colombel, Jean–Frédéric; Hébuterne, Xavier; Hofman, Paul; Naquet, Philippe; Galland, Franck

doi:10.1097/mib.0b013e3182a32b03

Cited by 41 publications

(38 citation statements)

References 29 publications

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“…Enhanced expression of VNN1 has been associated with multiple human diseases, including immune thrombocytopenia 25 , systemic lupus erythematosus 26 , and inflammatory bowel disease 27 , however, dysregulated VNN1 mRNA expression has not been reported in asthma. Consistent with this, the expression level of VNN1 in mouse lungs was not altered by repeated allergen or IL-13 in experimental models of asthma 28, 29 .…”

Section: Discussionmentioning

confidence: 99%

Vanin-1 expression and methylation discriminate pediatric asthma corticosteroid treatment response

Chang

Myers

et al. 2015

Journal of Allergy and Clinical Immunology

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Background There is considerable heterogeneity in asthma treatment response. Objective To identify biomarkers of corticosteroid treatment response in children with asthma and evaluate the utility and mechanistic basis of these biomarkers. Methods Children (5–18 years) presenting to the Emergency Department (ED) with an acute asthma exacerbation were recruited and followed during hospitalization. Nasal epithelial cells were collected upon presentation to the ED (T0) and 18–24 hours later (T1) and T1/T0 gene expression ratios were analyzed to identify genes associated with good and poor corticosteroid treatment response phenotypes. The utility of these genes in discriminating between systemic corticosteroid treatment response groups was then tested prospectively in a new cohort of patients. A gene candidate (VNN1) that consistently distinguished good versus poor response phenotypes was further studied in an experimental asthma model and VNN1 promoter methylation was measured by bisulfite pyrosequencing in patients. Results VNN1 mRNA expression changes were associated with systemic corticosteroid treatment response in children with acute asthma and VNN1 was required for optimal response to corticosteroid treatment in an experimental asthma model. A CpG site within the VNN1 promoter was differentially methylated between good versus poor treatment response groups and methylation at this site correlated with VNN1 mRNA expression. Conclusions We have identified a biological basis for poor corticosteroid treatment response that can be used to distinguish a subgroup of asthmatic children who respond poorly to systemic corticosteroid treatment. VNN1 contributes to corticosteroid responsiveness and changes in VNN1 nasal epithelial mRNA expression and VNN1 promoter methylation may be clinically useful biomarkers of treatment response in asthmatic children.

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Section: Discussionmentioning

confidence: 99%

Vanin-1 expression and methylation discriminate pediatric asthma corticosteroid treatment response

Chang

Myers

et al. 2015

Journal of Allergy and Clinical Immunology

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“…In addition, IL6ST and VNN1 are two target genes of has-miR-193a-5p. The polymorphisms of VNN1 gene is associated with susceptibility to inflammatory bowel diseases (39) and participates in the regulation of gut inflammation (40). …”

Section: Discussionmentioning

confidence: 99%

Involvement of MicroRNAs in Probiotics-Induced Reduction of the Cecal Inflammation by Salmonella Typhimurium

Chen

Tong

et al. 2017

Front. Immunol.

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The microRNAs (miRNAs) have been shown to play important roles in the development of the immune system and in regulation of host inflammation responses. Probiotics can effectively alleviate the inflammation caused by Salmonella in chickens. However, whether and how miRNAs are involved in modulation of the inflammation response in the gut of chickens have not been reported. In this study, the impact of a probiotics, Lactobacillus plantarum Z01 (LPZ01), was investigated on the cecal miRNAs and cytokine secretions in Salmonella Typhimurium (S. Typhimurium)-infected chickens at the age of 3 days. Newly hatched chicks were assigned to four groups (1): NC (basal diet) (2): S (basal diet + S. Typhimurium challenged) (3): SP (basal diet + S. Typhimurium challenged + LPZ01) (4): P (basal diet + LPZ01). In comparison with the S group, chicks in the SP group reduced the number of S. Typhimurium and had lower levels of interferon-γ and lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF) in ceca post challenge. Expression of 14 miRNAs was significantly affected by the presence of S. Typhimurium and/or lactobacillus. Five differential expression miRNAs (gga-miR-215-5p, gga-miR-3525, gga-miR-193a-5p, gga-miR-122-5p, and gga-miR-375) were randomly selected for confirmation by the RT-PCR. Predicted target genes of differentially expressed miRNAs were enriched in regulation of cAMP-dependent protein kinase activity, stress-activated MAPK cascade, immune system development and regulation of immune system process as well as in immune related pathways such as MAPK and Wnt signaling pathways. The relationship between changes of miRNAs and changes of cytokines was explored. Finally, 119 novel miRNAs were identified in 36 libraries totally. Identification of novel miRNAs significantly expanded the repertoire of chicken miRNAs and provided the basis for understanding the function of miRNAs in the host. Our results suggest that the probiotics reduce the inflammation of the S. Typhimurium infection in neonatal broiler chicks, at least partially, through regulation of miRNAs expression.

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“…XDH plays a major role in phagocytic killing47 and high expression levels are indicative of activated and infected macrophages in M paratuberculosis and is characteristic of oxidative stress. VNN1 is involved in cysteamine production, a major promotor of inflammation48 and polymorphisms of human VNN1 are linked to susceptibility to IBD49. FGF23 is expressed by activated macrophages, and elevated levels impair neutrophil recruitment50.…”

Section: Discussionmentioning

confidence: 99%

Pathways and Genes Associated with Immune Dysfunction in Sheep Paratuberculosis

Gossner¹,

Watkins

Chianini

2017

Sci Rep

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Multibacillary and paucibacillary paratuberculosis are both caused by Mycobacterium avium subspecies paratuberculosis. Multibacillary lesions are composed largely of infected epithelioid macrophages and paucibacillary lesions contain T cells but few bacteria. Multibacillary disease is similar to human lepromatous leprosy, with variable/high levels of antibody and a dysfunctional immune response. Animals with paucibacillary disease have high cell-mediated immunity and variable levels of antibody. This study aims to characterize the immunological dysfunction using TruSeq analysis of the ileocaecal lymph node that drains disease lesions. Immune dysfunction is highlighted by repression of TCR/CD3 genes, T cell co-receptors/co-stimulators, T cell activation and signal-transduction genes. Inflammation was an acute phase response and chronic inflammation, with little evidence of acute inflammation. The high levels of immunoglobulin and plasma cell transcripts is consistent with the anti-MAP antibody responses in paratuberculosis sheep. Also notable was the overwhelming reduction in mast cell transcripts, potentially affecting DC activation of the immune response. This study also shows that there were no fundamental differences in the gene expression patterns in multibacillary and paucibacillary disease, no shift in T cell genes from Th1 to Th2 pattern but rather an incremental decline into immune dysfunction leading to multibacillary pathology.

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Functional Polymorphisms in the Regulatory Regions of the VNN1 Gene Are Associated with Susceptibility to Inflammatory Bowel Diseases

Cited by 41 publications

References 29 publications

Vanin-1 expression and methylation discriminate pediatric asthma corticosteroid treatment response

Vanin-1 expression and methylation discriminate pediatric asthma corticosteroid treatment response

Involvement of MicroRNAs in Probiotics-Induced Reduction of the Cecal Inflammation by Salmonella Typhimurium

Pathways and Genes Associated with Immune Dysfunction in Sheep Paratuberculosis

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