Commensal-dependent expression of IL-25 regulates the IL-23–IL-17 axis in the intestine

Zaph, Colby; Du, Yurong; Saenz, Steven A.; Nair, Meera G.; Perrigoue, Jacqueline; Taylor, Betsy C.; Troy, Amy E.; Kobuley, Dmytro; Kastelein, Robert A.; Daniel, J.; Yu, Yimin; Artis, David

doi:10.1084/jem.20080720

Cited by 264 publications

(300 citation statements)

References 30 publications

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“…As shown in Fig. 8C, the expression of Il25, which is known to be induced by gut microflora (51), was decreased in the medial colon of cKO mice compared with WT mice. This decrease might be due to less efficient recognition of gut microflora in cKO mice, resulting in the decrease of Th2 cytokines and antimicrobial peptides.…”

Section: Induction Of Antimicrobial and Antiparasitic Peptides By Gutmentioning

confidence: 75%

Autophagy Protects against Colitis by the Maintenance of Normal Gut Microflora and Secretion of Mucus

Tsuboi

Nishitani

Takakura

et al. 2015

Journal of Biological Chemistry

102

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Background:The role of autophagy in colonic homeostasis is not clear. Results: Colonic epithelial cell-specific and autophagy-deficient mice showed exacerbation of colitis and abnormal gut microflora with less abundant antimicrobial peptide production and secretion of mucus. Conclusion: Autophagy protects against colitis by the maintenance of normal gut microflora and secretion of mucus. Significance: These findings may ultimately lead to an efficient intervention for inflammatory bowel diseases.

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Section: Induction Of Antimicrobial and Antiparasitic Peptides By Gutmentioning

confidence: 75%

Autophagy Protects against Colitis by the Maintenance of Normal Gut Microflora and Secretion of Mucus

Tsuboi

Nishitani

Takakura

et al. 2015

Journal of Biological Chemistry

102

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“…It has been reported that the differentiation of T H 17 cells in the colon of BALB/c mice is inhibited by IL-25 induced by the microbiota 39 . In accordance with these data, we found that the expression of Il25 in the ileal epithelium of germfree mice was markedly decreased as compared to SPF mice (Fig.…”

Section: Microbiota Represses Rorγt + Ilcs Through Il-25mentioning

confidence: 99%

RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota

et al. 2011

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“…IL-25 can be found in the large intestine (particularly in intestinal epithelial cells) and is involved in the maintenance of intestinal homeostasis, but is not expressed in germ-free mice. 12 The requirement of TGF-β and IL-4 for IL-25-dependent IL-9 production can be by-passed by the retroviral expression of IL-17RB in T cells or in transgenic mice in which IL-17RB expression is controlled by the CD4 promoter, thus suggesting that TGF-β and IL-4 render T cells IL-25-responsive by inducing IL-17RB expression. 11 It has been reported that a number of innate immune cells responsive to IL-25 (including monocytes and NKT cells) express functional IL-17RB, and that their treatment with IL-25 induces Th2 cytokine production.…”

Section: Introductionmentioning

confidence: 99%

Significance of serum Il-9 levels in inflammatory bowel disease

Defendenti

Sarzi-Puttini

Saibeni³

et al. 2015

Int J Immunopathol Pharmacol

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IL-9, which may be an inflammatory or regulatory cytokine, can be experimentally produced in a Th17 or modified Th2 context in the presence of T cell receptor (TCR) stimulation. The primary aim of this study was to measure serum IL-9 levels in patients with inflammatory bowel disease (IBD), and evaluate their relationships with the patients' clinical characteristics. The secondary aim was to determine the levels of interferon-γ (IFN (interferon)-γ), Th2 cytokines (IL-4, IL-5 and IL-13), and IL-6 in order to clarify the context of detectable peripheral cytokines in which IL-9 is produced.Venous blood samples of 43 IBD patients (20 with Crohn's disease [CD] and 23 with ulcerative colitis [UC]) were analysed by means of quantitative enzyme-linked immunosorbent assays using purified anti-human IL-4, IL-5, IL-13, IFN-γ, IL-9 and IL-6 antibodies, and the laboratory findings were statistically correlated with their clinical expression.None of the patients showed the peripheral presence of IL-4, IL-5 and IL-13. Forty (93%) were positive for IFN-γ, thus confirming the presence of Th1 in both UC and CD, and IFN-γ levels correlated with disease activity (P = 0.045). Eighteen patients (41%) were positive for IL-9, which was associated with a severe prognosis (P <0.001), and 72.2% of the IL-9-positive patients were also IL-6 positive. There was a significant correlation between disease severity and IL-9 in the CD patients (P <0.001), but not in the UC patients (P = 0.1).Our findings confirm the presence of common Th1 cytokines in UC and CD. However the IL-9 positivity indicates the presence of an alternative population of T cells that respond to antigen stimulation and condition the prognosis of IBD. The fact that the same serum IL-9 levels were differentially associated with clinical measures of CD and UC activity suggest that the same cytokine can be produced in different contexts.

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Commensal-dependent expression of IL-25 regulates the IL-23–IL-17 axis in the intestine

Cited by 264 publications

References 30 publications

Autophagy Protects against Colitis by the Maintenance of Normal Gut Microflora and Secretion of Mucus

Autophagy Protects against Colitis by the Maintenance of Normal Gut Microflora and Secretion of Mucus

RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota

Significance of serum Il-9 levels in inflammatory bowel disease

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