Crohn’s disease as an immunodeficiency
Reads0
Chats0
TLDR
The pathogenesis of Crohn’s disease has been regarded as the consequence of a dysregulated T-cell-mediated response to intestinal microbes, but recent molecular biological and clinical investigations indicate that CD is actually a primary immunodeficiency.Abstract:
The pathogenesis of Crohn's disease (CD) has widely been regarded as the consequence of a dysregulated T-cell-mediated response to intestinal microbes, and the majority of the worldwide research effort has focused on characterizing and treating the chronic inflammatory phase of the disease. However, recent molecular biological and clinical investigations indicate that CD is actually a primary immunodeficiency. At first counter-intuitive, the apparent paradox of a pathogenic innate immune defect can be linked mechanistically to the granulomatous chronic inflammation characteristic of the disease. Genome-wide association studies have corroborated the involvement of innate immune dysfunction in the pathogenesis of CD, but less than 20% of the heritable risk is accounted for. By contrast, in vitro and in vivo stimulation of the immune system has highlighted novel areas of interest that may lead to the development of targeted therapeutic and diagnostic tools.read more
Citations
More filters
Neutrophil apoptosis is delayed in patients with inflammatory bowel disease
Ann E. Brannigan,P. R. O'Connell,H. Hurley,Amanda O'Neill,Hugh R. Brady,John M. Fitzpatrick,R. W. G. Watson +6 more
TL;DR: In this article, the authors studied 20 patients with IBD, 13 with Crohn's disease, and 7 with ulcerative colitis, all of whom were undergoing intestinal resection for symptomatic disease.
Journal ArticleDOI
Granulocyte macrophage colony-stimulating factor ameliorates DSS-induced experimental colitis.
Satheesh K. Sainathan,Eyad M. Hanna,Qingqing Gong,Kumar S. Bishnupuri,Qizhi Luo,Marco Colonna,Frances V. White,Ed Croze,Courtney W. Houchen,Shrikant Anant,Brian K. Dieckgraefe +10 more
TL;DR: GM‐CSF is effective in the treatment of DSS colitis in a mechanism involving the 440c+ pDC population and exhibits synergy with pDC activators, such as microbial cytosine‐phosphate‐guanosine (CpG) DNA.
Clinical,microbiological, and immunological effects of fructo-oligosaccharide in patients with Crohn's disease
TL;DR: FOS supplementation increases faecal bifidobacteria concentrations and modifies mucosal dendritic cell function and appears to decrease Crohn's disease activity in a small open label trial and therefore warrants further investigation.
Journal ArticleDOI
Autophagy Attenuates the Adaptive Immune Response by Destabilizing the Immunologic Synapse
Manon E. Wildenberg,Manon E. Wildenberg,Anne Christine W. Vos,Simone C. Wolfkamp,Marjolijn Duijvestein,Auke P. Verhaar,Anje A. te Velde,Gijs R. van den Brink,Gijs R. van den Brink,Daniel W. Hommes,Daniel W. Hommes +10 more
TL;DR: Autophagy is induced upon formation of the immunologic synapse and negatively regulates T-cell activation, which might increase adaptive immunity in patients with Crohn's disease who carry ATG16L1 risk alleles.
Journal ArticleDOI
Impaired autophagy leads to abnormal dendritic cell–epithelial cell interactions
Caterina Strisciuglio,Marjolijn Duijvestein,Auke P. Verhaar,Anne Christine W. Vos,Gijs R. van den Brink,Gijs R. van den Brink,Daniel W. Hommes,Daniel W. Hommes,Manon E. Wildenberg,Manon E. Wildenberg +9 more
TL;DR: In intestinal DC-epithelial cell interactions, autophagy deficiency leads to decreased antigen sampling, increased DC maturation and a more pro-inflammatory type of DC.
References
More filters
Journal ArticleDOI
A human gut microbial gene catalogue established by metagenomic sequencing
Junjie Qin,Ruiqiang Li,Jeroen Raes,Manimozhiyan Arumugam,Kristoffer Sølvsten Burgdorf,Chaysavanh Manichanh,Trine Nielsen,Nicolas Pons,Florence Levenez,Takuji Yamada,Daniel R. Mende,Junhua Li,Junming Xu,Shaochuan Li,Dongfang Li,Jianjun Cao,Bo Wang,Huiqing Liang,Huisong Zheng,Yinlong Xie,Julien Tap,Patricia Lepage,Marcelo Bertalan,Jean-Michel Batto,Torben Hansen,Denis Le Paslier,Allan Linneberg,H. Bjørn Nielsen,Eric Pelletier,Pierre Renault,Thomas Sicheritz-Pontén,Keith Turner,Hongmei Zhu,Chang Yu,Shengting Li,Min Jian,Yan Zhou,Yingrui Li,Xiuqing Zhang,Songgang Li,Nan Qin,Huanming Yang,Jian Wang,Søren Brunak,Joël Doré,Francisco Guarner,Karsten Kristiansen,Oluf Pedersen,Julian Parkhill,Jean Weissenbach,Peer Bork,S. Dusko Ehrlich,Jun Wang +52 more
TL;DR: The Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals are described, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species.
Journal ArticleDOI
Finding the missing heritability of complex diseases
Teri A. Manolio,Francis S. Collins,Nancy J. Cox,David Goldstein,Lucia A. Hindorff,David J. Hunter,Mark I. McCarthy,Erin M. Ramos,Lon R. Cardon,Aravinda Chakravarti,Judy H. Cho,Alan E. Guttmacher,Augustine Kong,Leonid Kruglyak,Leonid Kruglyak,Elaine R. Mardis,Charles N. Rotimi,Montgomery Slatkin,David Valle,Alice S. Whittemore,Michael Boehnke,Andrew G. Clark,Evan E. Eichler,Greg Gibson,Jonathan L. Haines,Trudy F. C. Mackay,Steven A. McCarroll,Peter M. Visscher +27 more
TL;DR: This paper examined potential sources of missing heritability and proposed research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
Journal ArticleDOI
Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients
Harry Sokol,Bénédicte Pigneur,Laurie Watterlot,Omar Lakhdari,Luis G. Bermúdez-Humarán,Jean-Jacques Gratadoux,Sébastien Blugeon,Chantal Bridonneau,Jean-Pierre Furet,Gérard Corthier,Corinne Grangette,Nadia Vasquez,Philippe Pochart,Germain Trugnan,Ginette Thomas,Hervé M. Blottière,Joël Doré,Philippe Marteau,Philippe Seksik,Philippe Langella +19 more
TL;DR: The results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment and exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-κB activation and IL-8 production.
Journal ArticleDOI
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease
Jeffrey C. Barrett,Sarah Hansoul,Dan L. Nicolae,Judy H. Cho,Richard H. Duerr,John D. Rioux,John D. Rioux,Steven R. Brant,Mark S. Silverberg,Kent D. Taylor,M. Michael Barmada,Alain Bitton,Themistocles Dassopoulos,Lisa W. Datta,Todd Green,Anne M. Griffiths,Emily O. Kistner,Michael T. Murtha,Miguel Regueiro,Jerome I. Rotter,L. Philip Schumm,A. Hillary Steinhart,Stephan R. Targan,Ramnik J. Xavier,Cécile Libioulle,Cynthia Sandor,Mark Lathrop,Jacques Belaiche,Olivier Dewit,Ivo Gut,Simon Heath,Debby Laukens,Myriam Mni,Paul Rutgeerts,André Van Gossum,Diana Zelenika,Denis Franchimont,Jean-Pierre Hugot,Martine De Vos,Severine Vermeire,Edouard Louis,Lon R. Cardon,Carl A. Anderson,Hazel E. Drummond,Elaine R. Nimmo,Tariq Ahmad,Natalie J. Prescott,Clive M. Onnie,Sheila A. Fisher,Jonathan Marchini,Jilur Ghori,Suzannah Bumpstead,Rhian Gwilliam,Mark Tremelling,Panos Deloukas,John C. Mansfield,Derek P. Jewell,Jack Satsangi,Christopher G. Mathew,Miles Parkes,Michel Georges,Mark J. Daly,Mark J. Daly +62 more
TL;DR: The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1, which offer promise for informed therapeutic development.
Journal ArticleDOI
Bile salt biotransformations by human intestinal bacteria.
TL;DR: The potential exists for altering the bile acid pool by targeting key enzymes in the 7α/β-dehydroxylation pathway through the development of pharmaceuticals or sequestering bile acids biologically in probiotic bacteria, which may result in their effective removal from the host after excretion.