Gut-Busters: IL-17 Ain’t Afraid of No IL-23

Whibley, Natasha; Gaffen, Sarah L.

doi:10.1016/j.immuni.2015.10.001

Cited by 54 publications

(42 citation statements)

References 12 publications

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“…IL-23 inhibition had attenuated CD as well as promoting the development of the regulatory T cells (40). In another study, antibodies targeting IL-23 had ameliorated colitis (41). Results of this study are consistent with these observations because both IL-17A and IL-23 appear to perform dual roles in colitis.…”

Section: Thesupporting

confidence: 82%

Ccr6 Deficiency Attenuates Spontaneous Chronic Colitis in Winnie

Ranasinghe¹,

Fernando²,

Perera³

et al. 2019

Preprint

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The immunomodulatory behaviour of the CCR6/CCL20 axis on multi -system pathophysiology and molecular signalling was investigated at two clinically significant time points, using a Ccr6 - deficient mouse model of spontaneous colitis. Four groups of mice, (C57BL/6J, Ccr6-/- of C57BL/6J, Winnie x Ccr6 -/- and Winnie) were utilized and (I) colonic clinical parameters (2) histology of colon, spleen, kidney and liver (3) T and B lymphocyte distribution in the spleen and MLN by flowcytometry (5) colonic CCL20, PI3K and phosphorylated Akt expression by immunohistochemistry and (6) colonic cytokine expression by RT-PCR were evaluated. CCR6 influenced upregulation of inflammation in the spleen, liver and gut while renal histology remained unaffected. Marked focal lobular inflammation with reactive nuclear features were observed in hepatocytes and a significant neutrophil infiltration in red pulp with extra medullary hemopoiesis in the spleen existed in Winnie. These changes were considerably reduced in Winnie x Ccr6-/- with elevated goblet cell numbers and mucus production in the colonic epithelium. Results indicate that Ccr6- deficiency in the colitis model contributes towards resolution of disease. Our findings demonstrate an intricate networking role for CCR6 in immune activation, which is downregulated by Ccr6 deficiency, and could provide newer clinical therapies in colitis.

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Section: Thesupporting

confidence: 82%

Ccr6 Deficiency Attenuates Spontaneous Chronic Colitis in Winnie

Ranasinghe¹,

Fernando²,

Perera³

et al. 2019

Preprint

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“…We next confirmed that human OECs stimulated with IL-17 induced secretion of BD2, the human orthologue of murine BD3 (Fig 6D). Since clinical blockade of IL-17 is associated with impaired epithelial repair in the gut (Whibley and Gaffen, 2015), we asked whether IL-17 can protect from cell damage induced by C. albicans . However, IL-17 did not alter the cytotoxicity arising from C. albicans infection of cultured OECs, measured by secretion of lactate dehydrogenase (Fig 6E).…”

Section: Resultsmentioning

confidence: 99%

IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis

Conti

Bruno

Childs

et al. 2016

Cell Host & Microbe

156

196

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SUMMARY Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis (OPC) in mice and humans. However, the IL-17-responsive cell type(s) that mediate protection are unknown. Using radiation chimeras we were able to rule out a requirement for IL-17RA in the hematopoietic compartment. We saw remarkable concordance of IL-17-controlled gene expression in C. albicans-infected human oral epithelial cells (OECs) and in tongue tissue from mice with OPC. To interrogate the role of the IL-17R in OECs, we generated mice with conditional deletion of IL-17RA in superficial oral and esophageal epithelial cells (Il17raΔK13). Following oral Candida infection, Il17raΔK13 mice exhibited fungal loads and weight loss indistinguishable from Il17ra−/− mice. Susceptibility in Il17raΔK13 mice correlated with expression of the antimicrobial peptide β-defensin 3 (BD3, Defb3). Consistently, Defb3−/− mice were susceptible to OPC. Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of BD3expression.

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“…In fact, the intestinal epithelium damage caused by the IBD state is thought to trigger higher levels of FGF-2, a propagator of ISC regeneration, which works with IL-17Ato promote mucosal healing and intestinal epithelial cell proliferation (Brockmann et al, 2017; Houchen et al, 1999). Also, in clinical trials and studies with colitis mouse models, anti-IL-17A treatments aggravate IBD-associated symptoms, suggesting that IL-17A may play a role in reducing intestinal inflammation and promote gut healing (Whibley and Gaffen, 2015). TNFα has been previously reported to be chronically elevated in IBD patients, and TNFα inhibitors, such as infliximab and adalimumab, have long been established as effective treatments for IBD patients (Lichtenstein, 2013).…”

Section: Discussionmentioning

confidence: 99%

Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology

et al. 2019

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SUMMARY Dietary interventions are potentially effective therapies for inflammatory bowel diseases (IBDs). We tested the effect of 4-day fasting-mimicking diet (FMD) cycles on a chronic dextran sodium sulfate (DSS)-induced murine model resulting in symptoms and pathology associated with IBD. These FMD cycles reduced intestinal inflammation, increased stem cell number, stimulated protective gut microbiota, and reversed intestinal pathology caused by DSS, whereas water-only fasting increased regenerative and reduced inflammatory markers without reversing pathology. Transplants of Lactobacillus or fecal microbiota from DSS- and FMD-treated mice reversed DSS-induced colon shortening, reduced inflammation, and increased colonic stem cells. In a clinical trial, three FMD cycles reduced markers associated with systemic inflammation. The effect of FMD cycles on microbiota composition, immune cell profile, intestinal stem cell levels and the reversal of pathology associated with IBD in mice, and the anti-inflammatory effects demonstrated in a clinical trial show promise for FMD cycles to ameliorate IBD-associated inflammation in humans.

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Gut-Busters: IL-17 Ain’t Afraid of No IL-23

Cited by 54 publications

References 12 publications

Ccr6 Deficiency Attenuates Spontaneous Chronic Colitis in Winnie

Ccr6 Deficiency Attenuates Spontaneous Chronic Colitis in Winnie

IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis

Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology

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