The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Epithelial-derived IL-18 regulates Th17 cell differentiation and Foxp3+ Treg cell function in the intestine
Open accessAbstract
Elevated levels of interleukin-18 (IL-18) are found in many chronic inflammatory disorders, including inflammatory bowel disease (IBD), and polymorphisms in the IL18R1–IL18RAP locus are associated with IBD susceptibility. IL-18 is an IL-1 family cytokine that has been proposed to promote barrier function in the intestine, but the effects of IL-18 on intestinal CD4+ T cells are poorly understood. Here we demonstrate that IL-18R1 expression is enhanced on both effector and regulatory CD4+ T cells in the intestinal lamina propria, with T helper type 17 (Th17) cells exhibiting particularly high levels. We further show that, during steady state, intestinal epithelial cells constitutively secrete IL-18 that acts directly on IL-18R1-expressing CD4+ T cells to limit colonic Th17 cell differentiation, in part by antagonizing IL-1R1 signaling. In addition, although IL-18R1 is not required for colonic Foxp3+ regulatory T (Treg) cell differentiation, we found that IL-18R1 signaling was critical for Foxp3+ Treg cell–mediated control of intestinal inflammation, where it promoted the expression of key Treg effector molecules. Thus IL-18 is a key epithelial-derived cytokine that differentially regulates distinct subsets of intestinal CD4+ T cells during both homeostatic and inflammatory conditions, a finding with potential implications for treatment of chronic inflammatory disorders.
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Cites
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Cited by
The immune response to Prevotella bacteria in chronic inflammatory disease
Larsen, J. M. (2017) · Immunology · doi:10.1111/imm.12760 · Cited by 1,343
Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity
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A Distinct Function of Regulatory T Cells in Tissue Protection
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Interactions Between the Gut Microbiota and the Host Innate Immune Response Against Pathogens
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Nowarski, R., Jackson, R., & Flavell, R. A. (2017) · Cell · doi:10.1016/j.cell.2016.11.040 · Cited by 191
Metadata
- Authors
- Harrison, O. J., Srinivasan, N., Pott, J., Schiering, C., Krausgruber, T., Ilott, N. E., & Maloy, K. J.
- Venue
- Mucosal Immunology
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 8
- Issue
- 6
- Pages
- 1226-1236
- ISSN
- 1933-0219 (ISSN-L)
- OpenAlex
- W2133167870
- Cited by
- 239
- References
- 11
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- bronze
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