Functional screen of inflammatory bowel disease genes reveals key epithelial functions View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-11-11

AUTHORS

Jessy Carol Ntunzwenimana, Gabrielle Boucher, Jean Paquette, Hugues Gosselin, Azadeh Alikashani, Nicolas Morin, Claudine Beauchamp, Louise Thauvette, Marie-Ève Rivard, Frédérique Dupuis, Sonia Deschênes, Sylvain Foisy, Frédéric Latour, Geneviève Lavallée, Mark J. Daly, Ramnik J. Xavier, Guy Charron, Philippe Goyette, John D. Rioux

ABSTRACT

BackgroundGenetic studies have been tremendously successful in identifying genomic regions associated with a wide variety of phenotypes, although the success of these studies in identifying causal genes, their variants, and their functional impacts has been more limited.MethodsWe identified 145 genes from IBD-associated genomic loci having endogenous expression within the intestinal epithelial cell compartment. We evaluated the impact of lentiviral transfer of the open reading frame (ORF) of these IBD genes into the HT-29 intestinal epithelial cell line via transcriptomic analyses. By comparing the genes in which expression was modulated by each ORF, as well as the functions enriched within these gene lists, we identified ORFs with shared impacts and their putative disease-relevant biological functions.ResultsAnalysis of the transcriptomic data for cell lines expressing the ORFs for known causal genes such as HNF4a, IFIH1, and SMAD3 identified functions consistent with what is already known for these genes. These analyses also identified two major clusters of genes: Cluster 1 contained the known IBD causal genes IFIH1, SBNO2, NFKB1, and NOD2, as well as genes from other IBD loci (ZFP36L1, IRF1, GIGYF1, OTUD3, AIRE and PITX1), whereas Cluster 2 contained the known causal gene KSR1 and implicated DUSP16 from another IBD locus. Our analyses highlight how multiple IBD gene candidates can impact on epithelial structure and function, including the protection of the mucosa from intestinal microbiota, and demonstrate that DUSP16 acts a regulator of MAPK activity and contributes to mucosal defense, in part via its regulation of the polymeric immunoglobulin receptor, involved in the protection of the intestinal mucosa from enteric microbiota.ConclusionsThis functional screen, based on expressing IBD genes within an appropriate cellular context, in this instance intestinal epithelial cells, resulted in changes to the cell’s transcriptome that are relevant to their endogenous biological function(s). This not only helped in identifying likely causal genes within genetic loci but also provided insight into their biological functions. Furthermore, this work has highlighted the central role of intestinal epithelial cells in IBD pathophysiology, providing a scientific rationale for a drug development strategy that targets epithelial functions in addition to the current therapies targeting immune functions. More... »

PAGES

181

References to SciGraph publications

  • 2006-12-31. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1 in NATURE GENETICS
  • 2020-02-27. Moving towards a systems-based classification of innate immune-mediated diseases in NATURE REVIEWS RHEUMATOLOGY
  • 2001-05. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease in NATURE
  • 2011-06-15. Genetics and pathogenesis of inflammatory bowel disease in NATURE
  • 2006-07. Intracellular pattern recognition receptors in the host response in NATURE
  • 2015-07-20. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations in NATURE GENETICS
  • 2019-12-18. Somatic inflammatory gene mutations in human ulcerative colitis epithelium in NATURE
  • 2013-12-23. Regulation of type I interferon responses in NATURE REVIEWS IMMUNOLOGY
  • 2017-06-28. Fine-mapping inflammatory bowel disease loci to single-variant resolution in NATURE
  • 2018-04-24. Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study in NATURE COMMUNICATIONS
  • 2011-10-09. Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease in NATURE GENETICS
  • 2011-03-30. Regulation of the polymeric immunoglobulin receptor by the classical and alternative NF-κB pathways in intestinal epithelial cells in MUCOSAL IMMUNOLOGY
  • 2016-08-09. A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis in NATURE COMMUNICATIONS
  • 2019-12-18. Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis in NATURE
  • 2015-08-17. Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis in NATURE CELL BIOLOGY
  • 2014-10-29. Genetic and epigenetic fine mapping of causal autoimmune disease variants in NATURE
  • 2010-08-09. The role of secretory antibodies in infection immunity in NATURE REVIEWS MICROBIOLOGY
  • 2007-04-15. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis in NATURE GENETICS
  • 2015-01-05. High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis in NATURE GENETICS
  • 2001-05. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease in NATURE
  • 2015-12-21. The tumor suppressor PTEN has a critical role in antiviral innate immunity in NATURE IMMUNOLOGY
  • 2019-05-02. Tristetraprolin specifically regulates the expression and alternative splicing of immune response genes in HeLa cells in BMC IMMUNOLOGY
  • 2005-09-14. Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks in BMC BIOINFORMATICS
  • 2008-08-08. Altered gene expression in highly purified enterocytes from patients with active coeliac disease in BMC GENOMICS
  • 2018-06-21. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes in NATURE COMMUNICATIONS
  • 2008-08-24. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease in NATURE GENETICS
  • 2012-10-31. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease in NATURE
  • 2009-11-15. Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region in NATURE GENETICS
  • 2017-01-09. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease in NATURE GENETICS
  • 2017-01-09. Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7 in NATURE GENETICS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13073-021-00996-7

    DOI

    http://dx.doi.org/10.1186/s13073-021-00996-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1142503440

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34758847


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