Increased numbers of innate lymphoid cells in patients with inflammatory bowel disease

Alessandra Geremia

Andoh

Baljit Singh

Barrett

Bull

Buonocore

Carolina V. Arancibia-Cárcamo

Cella

Crellin

Cupedo

Di Sabatino

Duerr

Eberl

Elson

Fiona Powrie

Fisher

Franke

Fujino

Izcue

Kaser

Kleinschek

Kobayashi

Kwon

Luci

Mebius

Myles P.P. Fleming

Neil J. Mortensen

Nigel Rust

Sanos

Satoh-Takayama

Simon P.L. Travis

Takatori

Takayama

Uhlig

Wehkamp

Wilson

English

PubMed

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.</jats:p

Crossref

The Journal of Experimental Medicine

IL-23–responsive innate lymphoid cells are increased in inflammatory bowel disease

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

Geremia, Alessandra

Arancibia-Cárcamo, CV

Fleming, MP

Rust, N

Singh, B

Mortensen, NJ

Travis, SP

Powrie, F

Oxford University Research Archive

IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease.

Geremia, A

Oxford University Research Archive (ORA)

A genome-wide association study identifies IL23R as an inflammatory bowel disease gene.

Brief Definitive Report killer cells in the intestinal mucosa of patients with Crohn’s disease.

Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation.

Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease.

Human beta-defensin 2 but not beta-defensin 1 is expressed preferentially in colonic mucosa of inflammatory bowel disease.

Human NKp44+IL-22+ cells and LTi-like cells constitute a stable RORC+ lineage distinct from conventional natural killer cells.

Increased expression of interleukin 17 in inflammatory bowel disease.

Influence of the transcription factor RORgammat on the development of NKp46+ cell populations in gut

Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts.

Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain.

Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense.

Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice.

Replication of signals from recent studies of Crohn’s disease identifies previously unknown disease loci for ulcerative colitis.

Targeting gut T cell Ca2+ release-activated Ca2+ channels inhibits T cell cytokine production and T-box transcription factor T-bet in inflammatory bowel disease.

http://jem.rupress.org/content/jem/208/6/1127.full.pdf

IL-23–responsive innate lymphoid cells are increased in inflammatory bowel disease

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Oxford University Research Archive

Oxford University Research Archive (ORA)