IL-23 is essential for T cell–mediated colitis and promotes inflammation via IL-17 and IL-6

Yen, David; Cheung, Jeanne; Scheerens, Heleen; Poulet, Frederique M.; McClanahan, Terrill K.; McKenzie, Brent; Kleinschek, Melanie A.; Owyang, Alex M.; Mattson, Jeanine D.; Blumenschein, Wendy M.; Murphy, Erin; Sathe, Manjiri; Daniel, J.; Kastelein, Robert A.; Rennick, Donna

doi:10.1172/jci21404

Cited by 1,378 publications

(1,085 citation statements)

References 40 publications

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“…IL-23 has been reported to be essential for the development of autoimmunity in mouse models, and current data suggest that this is due to the production of IL-17 (6,(8)(9)(10)26,39). We found that naive CD4ϩ T cells expressed low levels of IL-23R mRNA compared with memory CD4ϩ T cells (Figure 4a).…”

Section: Il-23 Up-regulation Of Il-23r and Enhancement Of Il-17 Produmentioning

confidence: 50%

“…The current view of mouse Th17 development is that TGF␤1 and IL-6 are the key cytokines that initiate the differentiation process and that IL-23 plays an essential role in the expansion and maintenance of this lineage. Support for the notion of an IL-23/IL-17 axis has been provided by a number of models of autoimmunity (6,(8)(9)(10)(11)26,39,(44)(45)(46), but despite these compelling data in mice, a systematic analysis of human Th17 differentiation from naive cells has not yet been undertaken.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, anti-p40 antibody is efficacious in the treatment of Crohn's disease (7). Although these effects were initially misattributed to interference with the actions of IL-12, using specific deletion of IL-23 (p19 Ϫ/Ϫ mice), it is now recognized that IL-23 (and not IL-12) is the culprit, at least in many of the animal models (8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

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Distinct regulation of interleukin‐17 in human T helper lymphocytes

Chen¹,

Tato²,

Muul³

et al. 2007

Arthritis & Rheumatism

312

280

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Section: Il-23 Up-regulation Of Il-23r and Enhancement Of Il-17 Produmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Distinct regulation of interleukin‐17 in human T helper lymphocytes

Chen¹,

Tato²,

Muul³

et al. 2007

Arthritis & Rheumatism

312

280

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“…The involvement of Th17 lymphocytes, which produce IL-6/IL-17, has been demonstrated in the development the inflammatory process in CD (Fujino et al 2003;Yen et al 2006). On the other hand, in UC the inflammatory response seems to be dominated by Th2 lymphocytes, which secrete high amounts of IL-5 and IL-13 (Fuss et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory cytokines and IL-10 in inflammatory bowel disease and colorectal cancer patients

Szkaradkiewicz

Marciniak

Chudzicka-Strugała

et al. 2009

Arch. Immunol. Ther. Exp.

107

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Introduction: The aim of the study was to describe the levels of circulating monocyte/macrophage pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8) and an anti-inflammatory cytokine (IL-10) in inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients and healthy controls. Materials and Methods:The study was conducted on 15 healthy individuals, 20 patients with ulcerative colitis (UC), 12 with Crohn's disease (CD), and 15 with CRC (Dukes' stage B). Blood serum cytokine levels were measured by ELISA. Results: The patients with UC had significantly higher levels of the pro-inflammatory cytokines and of circulating IL-10 than the healthy controls. The patients with CD and CRC had the same specific pattern of serum cytokines of significantly elevated levels of the pro-inflammatory cytokines, but the IL-10 levels were within the range found in the healthy individuals. Conclusions: Thus our results demonstrate that both IBD and CRC are linked with an intensified production of a wide array of monocyte/macrophage pro-inflammatory cytokines which is not accompanied by elevated levels of circulating IL-10, except for its insufficiently inhibitory elevation in UC patients.

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“…An IL‐12‐driven Th1 response may dominate during the early stages of CD, implying that susceptibility to IL‐12‐mediated modulation is strongly dependent on the stage of the disease,16 although activities that have been attributed to IL‐12 in the past may have been mediated by IL‐23 17. Several studies have now demonstrated an important role for Th17 cells in intestinal inflammation 18, 19…”

Section: Discussionmentioning

confidence: 99%

Measurement of IL‐12 (p40, p35), IL‐23p19, and IFN‐γ mRNA in Duodenal Biopsies of Cats with Inflammatory Enteropathy

Waly

Peters

Day

et al. 2013

Veterinary Internal Medicne

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BackgroundDietary hypersensitivity and inflammatory bowel disease (IBD) are important causes of chronic vomiting and diarrhea in cats. IL‐23 has been recently found to be a key factor in the immunopathogenesis of IBD in humans but the involvement in IBD has not been investigated in cats.Hypothesis/ObjectivesExpression of genes encoding Il‐12p35 and p40, IL‐23p19, and IFN‐γ may be up‐regulated in duodenal biopsy specimens taken from cats with histologic evidence of inflammation.Animals and MethodsDuodenal biopsy specimens were collected from control cats (n = 21) and cats with inflammatory enteropathy (n = 13). Routine histopathology, immunohistochemistry (IHC), and qRT‐PCR were used to assess expression of MHC class II and to measure gene transcripts encoding the p35, p40, and p19 subunits of the IL‐12 family of cytokines and IFN‐γ.ResultsThere were significant differences in expression of mRNA encoding IL‐12p35 and IL‐23p19 between healthy cats and cats with inflammatory enteropathy. IL‐12p35 mRNA was lower in the duodenal mucosa of cats with inflammatory enteropathy compared with the mucosa of healthy cats (P = .001). In contrast, IL‐23p19 mRNA expression was higher in duodenal biopsy specimens from cats with inflammatory enteropathy than in those from healthy controls (P = .001). There was no difference in expression of IL‐12p40 and IFN‐γ mRNA (P > .05). The majority of cats with inflammatory enteropathy had histologic evidence of moderate to severe colitis (score 2).Conclusions and Clinical ImportanceThe results of this preliminary study suggest that IL‐23 plays a role in the pathogenesis of feline inflammatory enteropathy.

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IL-23 is essential for T cell–mediated colitis and promotes inflammation via IL-17 and IL-6

Cited by 1,378 publications

References 40 publications

Distinct regulation of interleukin‐17 in human T helper lymphocytes

Distinct regulation of interleukin‐17 in human T helper lymphocytes

Proinflammatory cytokines and IL-10 in inflammatory bowel disease and colorectal cancer patients

Measurement of IL‐12 (p40, p35), IL‐23p19, and IFN‐γ mRNA in Duodenal Biopsies of Cats with Inflammatory Enteropathy

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