IL-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability
By Jacob S. Lee, C. Tato, B. Joyce-Shaikh, Fatih Gulan, Corinne Cayatte, Yi Chen, W. Blumenschein, Michael Judo, Kevin Chen, G. Ayanoglu and 3 more. Immunity, 2015
712 citations recorded by the source corpus.
Whether IL-17A has pathogenic and/or protective roles in the gut mucosa is controversial and few studies have analyzed specific cell populations for protective functions within the inflamed colonic tissue. Here we provide evidence for IL-17A dependent regulation of the tight junction protein occludin during epithelial injury that limits excessive permeability and maintains barrier integrity. Analysis of epithelial cells showed that in the absence of Act-1 signaling, the protective effect of IL-17A was abrogated and inflammation was enhanced. We demonstrate that following acute intestinal injury, IL-23R+ RORγt+ γδ T cells in the colonic lamina propria are the primary producers of early, gut-protective IL-17A, over other cell populations such as memory Th17 cells and ILC3. This production of IL-17A was IL-23 independent, leaving protective IL-17 intact in the absence of IL-23. These results suggest that IL-17 producing resident γδ T cells are important for the maintenance, and protectionof epithelial barriers in the intestinal mucosa.
Subfields: Dermatology, Immunology
View Paper: https://www.semanticscholar.org/paper/dcfae930aa0dd143c5109cf1c9513389686811a4
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Citations in the corpus
- Psoriasis Pathogenesis and Treatment (2019, background): “Alternatively, γδ T cells are able to produce IL-17A independently of the IL-23 stimulus [66].”
- Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. (2019, background): “It is notable that IL-17A dependent intestinal barrier function is IL-23 independent, indicating this important host defense function will be maintained in IL-23 targeting {Maxwell, 2015 #361;Lee, 2015 #360}.”
- The IL-17 family of cytokines in health and disease (2019, background): “Consistently, mouse studies showed that colitis-associated epithelial injury and intestinal leakage can be exacerbated in absence of IL-17 signaling, and revealed that IL-17 serves a beneficial role in the intestinal epithelium by helping to maintain the epithelial tight-junction barrier during infl”
- Negative Effects of a High-Fat Diet on Intestinal Permeability: A Review. (2019, background): “For example, intestines of mice fed an HFD showed markedly reduced IL17, a cytokine that promotes gut barrier TJ organization via Act1-mediated association of OCLN with F-actin (61).”
- Structural activation of pro-inflammatory human cytokine IL-23 by cognate IL-23 receptor enables recruitment of the shared receptor IL-12Rβ1 (2017, background): “Nevertheless, the IL-23-IL-17 axis appears to entail differential roles for the two cytokines in intestinal immunoregulation, as their inhibition in Crohn’s disease yields opposing effects, with IL-23 emerging as the therapeutically relevant target (Lee et al., 2015; Maxwell et al., 2015).”