Interleukin-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability

Lee, Jacob S.; Tato, Cristina M.; Joyce-Shaikh, Barbara; Gulen, Muhammet F.; Cayatte, Corinne; Chen, Yi; Blumenschein, Wendy M.; Judo, Michael; Ayanoglu, Gulesi; McClanahan, Terrill K.; Li, Xiaoxia; Cua, Daniel J.

doi:10.1016/j.immuni.2015.10.019

Cited by 140 publications

(183 citation statements)

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“…and Maxwell et al . reveal a protective function of IL-17 through maintenance of intestinal barrier integrity, helping to explain this dichotomy (Lee et al, 2015; Maxwell et al, 2015). …”

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confidence: 99%

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

Whibley

Gaffen

2015

Immunity

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“…and Maxwell et al . reveal a protective function of IL-17 through maintenance of intestinal barrier integrity, helping to explain this dichotomy (Lee et al, 2015; Maxwell et al, 2015). …”

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confidence: 99%

“…Tregs are also associated with protection against colitis. Indeed, colitis symptoms upon antibody treatment correlated closely with changes in Foxp3 + Treg cells (Lee et al, 2015). Recently, it was proposed that Th17 and Treg cells cooperate in the gut to promote repair of the damaged epithelial barrier during colitis (Song et al, 2015).…”

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confidence: 99%

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

Whibley

Gaffen

2015

Immunity

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“…39,40 However, gut Th17 cells or IL-17 itself is also important for maintaining intestinal immune responses and barrier function. 41,42 The contribution of IL-17-producing neutrophils to IBD development added a more innate source for IL-17 in the pathogenesis of IBD. Furthermore, Wip1-deficient neutrophils produced more IL-17, so adoptive transfer of Wip1-deficient neutrophils promoted more severe clinical colitis symptoms and pathology including bodyweight loss, DAI score, decreased colon length, and hematoxylin and eosin staining.…”

Section: Discussionmentioning

confidence: 99%

Phosphatase Wip1 Masters IL-17–producing Neutrophil-mediated Colitis in Mice

Wang

et al. 2016

Inflammatory Bowel Diseases

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Wild-type p53-induced phosphatase 1 (Wip1) is currently believed to be a promising drug target for cancer therapy. Our recent studies showed that deletion of Wip1 remarkably promoted neutrophil inflammatory response. Whether Wip1 is involved in the regulation of inflammatory bowel disease is unknown. In the present study, we found that Wip1 knockout (KO) mice were more susceptible to colitis induced by dextran sulphate sodium (DSS) than wild-type mice as substantiated by the lower mouse survival ratio, rapid bodyweight loss, increased disease activity index, shorter colon length, and more severe pathology of colons in Wip1KO mice. Using full bone marrow chimera mouse models, we demonstrated that Wip1 intrinsically controls inflammatory response of immune cells. Deletion of IL-17 (Wip1/IL-17 double KO mice) significantly rescued the pathology in Wip1KO mice. Neutrophils of DSS-treated wild-type and Wip1KO mice expressed significantly higher IL-17. After adoptive transfer of sorted Wip1KO or double KO neutrophils into IL-17KO mice, mice receiving double KO neutrophils were more resistant to DSS-induced colitis than mice receiving Wip1KO neutrophils. These data collectively indicate that Wip1 modulates host sensitivity to colitis by intrinsically regulating immune cells. The enhanced IL-17 expression in neutrophils contributed to the increased sensitivity and severity of colitis in Wip1KO mice. Thus, Wip1 may be used as a drug target to treat colitis.

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“…Reciprocally, activated ILC2s secrete IL‐13, which promotes tuft and goblet cell differentiation and parasite clearance . The signature cytokines secreted by Th17 cells (IL‐17A, IL‐17F and IL‐22) can also induce IEC‐mediated AMP secretion and reinforce IEC tight junctions . In addition, production of fibroblast growth factor 2 (FGF2) by Treg cells has recently been shown to synergize with IL‐17 to enhance mechanisms of intestinal epithelial repair .…”

Section: Iec–immune Cell Crosstalkmentioning

confidence: 99%

Intestinal epithelial cells: at the interface of the microbiota and mucosal immunity

2019

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Summary The intestinal epithelium forms a barrier between the microbiota and the rest of the body. In addition, beyond acting as a physical barrier, the function of intestinal epithelial cells (IECs) in sensing and responding to microbial signals is increasingly appreciated and likely has numerous implications for the vast network of immune cells within and below the intestinal epithelium. IECs also respond to factors produced by immune cells, and these can regulate IEC barrier function, proliferation and differentiation, as well as influence the composition of the microbiota. The mechanisms involved in IEC–microbe–immune interactions, however, are not fully characterized. In this review, we explore the ability of IECs to direct intestinal homeostasis by orchestrating communication between intestinal microbes and mucosal innate and adaptive immune cells during physiological and inflammatory conditions. We focus primarily on the most recent findings and call attention to the numerous remaining unknowns regarding the complex crosstalk between IECs, the microbiota and intestinal immune cells.

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Interleukin-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability

Cited by 140 publications

References 0 publications

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

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

Phosphatase Wip1 Masters IL-17–producing Neutrophil-mediated Colitis in Mice

Intestinal epithelial cells: at the interface of the microbiota and mucosal immunity

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