IL-23–responsive innate lymphoid cells are increased in inflammatory bowel disease
Alessandra Geremia,Carolina V. Arancibia-Cárcamo,M Fleming,Nigel A. Rust,Baljit Singh,Neil Mortensen,Simon Travis,Fiona Powrie +7 more
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TLDR
Increased numbers of innate lymphoid cells in patients with inflammatory bowel disease are found to be associated with better prognosis and decreased likelihood of long-term disease progression.Abstract:
Results of experimental and genetic studies have highlighted the role of the IL-23/IL-17 axis in the pathogenesis of inflammatory bowel disease (IBD). IL-23–driven inflammation has been primarily linked to Th17 cells; however, we have recently identified a novel population of innate lymphoid cells (ILCs) in mice that produces IL-17, IL-22, and IFN-γ in response to IL-23 and mediates innate colitis. The relevance of ILC populations in human health and disease is currently poorly understood. In this study, we have analyzed the role of IL-23–responsive ILCs in the human intestine in control and IBD patients. Our results show increased expression of the Th17-associated cytokine genes IL17A and IL17F among intestinal CD3− cells in IBD. IL17A and IL17F expression is restricted to CD56− ILCs, whereas IL-23 induces IL22 and IL26 in the CD56+ ILC compartment. Furthermore, we observed a significant and selective increase in CD127+CD56− ILCs in the inflamed intestine in Crohn’s disease (CD) patients but not in ulcerative colitis patients. These results indicate that IL-23–responsive ILCs are present in the human intestine and that intestinal inflammation in CD is associated with the selective accumulation of a phenotypically distinct ILC population characterized by inflammatory cytokine expression. ILCs may contribute to intestinal inflammation through cytokine production, lymphocyte recruitment, and organization of the inflammatory tissue and may represent a novel tissue-specific target for subtypes of IBD.read more
Citations
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Journal ArticleDOI
Intestinal epithelial cells: regulators of barrier function and immune homeostasis
Lance W. Peterson,David Artis +1 more
TL;DR: This Review provides a comprehensive overview of how IECs maintain host–commensal microbial relationships and immune cell homeostasis in the intestine.
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Cytokines in inflammatory bowel disease
TL;DR: The role of cytokines produced by innate and adaptive immune cells, as well as their relevance to the future therapy of IBD are discussed.
Journal ArticleDOI
Crohn's disease
TL;DR: An physician-oriented overview of Crohn's disease in adults is provided, ranging from epidemiology and cause to clinical diagnosis, natural history, patient stratification and clinical management, and ending with an overview of emerging therapies and future directions for research.
Journal ArticleDOI
Immunopathogenesis of IBD: current state of the art
TL;DR: Current knowledge of the classic immune components are reviewed and the concept of IBD immunopathogenesis is expanded to include various cells, mediators and pathways that have not been traditionally associated with disease mechanisms, but that profoundly affect the overall intestinal inflammatory process.
Journal ArticleDOI
Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues
Jochem H. Bernink,Charlotte P. Peters,Marius Munneke,Anje A. te Velde,Sybren L. Meijer,Kees Weijer,Hulda S. Hreggvidsdottir,Sigrid E.M. Heinsbroek,Nicolas Legrand,Nicolas Legrand,Christianne J. Buskens,Willem A. Bemelman,Jenny Mjösberg,Jenny Mjösberg,Hergen Spits +14 more
TL;DR: The frequency of the ILC1 subset was much higher in inflamed intestine of people with Crohn's disease, which indicated a role for these IFN-γ-producing I LC1 cells in the pathogenesis of gut mucosal inflammation.
References
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Journal ArticleDOI
A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene
Richard H. Duerr,Kent D. Taylor,Steven R. Brant,Steven R. Brant,John D. Rioux,John D. Rioux,Mark S. Silverberg,Mark J. Daly,Mark J. Daly,A. Hillary Steinhart,Clara Abraham,Miguel Regueiro,Anne M. Griffiths,Themistocles Dassopoulos,Alain Bitton,Huiying Yang,Stephan R. Targan,Lisa W. Datta,Emily O. Kistner,L. Philip Schumm,Annette Lee,Peter K. Gregersen,M. Michael Barmada,Jerome I. Rotter,Dan L. Nicolae,Judy H. Cho +25 more
TL;DR: A highly significant association is found between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23, which prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.
Journal ArticleDOI
Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain
Daniel J. Cua,Jonathan P Sherlock,Yi Chen,Craig A. Murphy,Barbara L. Joyce,Brian W. P. Seymour,Linda Lucian,Wayne To,Sylvia Kwan,Tatyana Churakova,Sandra Zurawski,Maria T. Wiekowski,Sergio A. Lira,Sergio A. Lira,Daniel M. Gorman,Robert A. Kastelein,Jonathon D. Sedgwick +16 more
TL;DR: It is shown that the perceived central role for IL-12 in autoimmune inflammation, specifically in the brain, has been misinterpreted and that IL-23, and not IL- 12, is the critical factor in this response.
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
Development, cytokine profile and function of human interleukin 17-producing helper T cells
Nicholas J. Wilson,Katia Boniface,Jason R. Chan,Brent S. McKenzie,Wendy M. Blumenschein,Jeanine D. Mattson,Beth Basham,Kathleen M. Smith,Taiying Chen,Franck Morel,Jean-Claude Lecron,Robert A. Kastelein,Daniel J. Cua,Terrill K. McClanahan,Edward P. Bowman,Rene de Waal Malefyt +15 more
TL;DR: It is demonstrated that IL-23 and IL-1β induced the development of human and mouse TH-17 cells expressing IL-17A,IL-17F, IL-22, Il-26, interferon-γ, the chemokine CCL20 and transcription factor RORγt, and that human TH- 17 cells may regulate innate immunity in epithelial cells.
Journal ArticleDOI
Increased expression of interleukin 17 in inflammatory bowel disease.
Sanae Fujino,Akira Andoh,Shigeki Bamba,Atsuhiro Ogawa,Kazunori Hata,Yoshio Araki,Tadao Bamba,Yoshihide Fujiyama +7 more
TL;DR: It is likely that IL-17 expression in IBD may be associated with altered immune and inflammatory responses in the intestinal mucosa and increased in patients with inflammatory bowel disease.
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