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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
IL-17 produced by Paneth cells drives TNF-induced shock
Nozomi Takahashi1, Ineke Vanlaere, Riet de Rycke
1Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, Netherlands.
The Journal of Experimental Medicine
|July 30, 2008
Summary
Interleukin-17 (IL-17) exacerbates lethal tumor necrosis factor (TNF) responses by promoting inflammation. Blocking IL-17 or its receptor protects against TNF-induced shock and organ failure, revealing a novel role for Paneth cells in acute inflammation.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Tumor necrosis factor (TNF) exhibits potent anti-tumor effects but can trigger fatal systemic inflammatory response syndrome.
- Interleukin-17 (IL-17), a pro-inflammatory cytokine primarily from T cells, is implicated in inflammatory processes.
Purpose of the Study:
- To investigate the role of IL-17 in TNF-induced systemic inflammation and shock.
- To identify the cellular source and mechanism of IL-17 release during acute inflammation.
Main Methods:
- Mice were treated with antiserum against IL-17 or genetically modified to lack the IL-17 receptor (Il17r).
- Serum cytokine levels (IL-6), nitric oxide metabolites, and leukocyte infiltration in the small intestine were measured after TNF challenge.
- Electron microscopy was used to visualize IL-17 localization and release from Paneth cells.
Main Results:
- Blocking IL-17 or Il17r significantly protected mice from lethal TNF challenge.
- Mice deficient in IL-17R showed reduced TNF-induced IL-6, nitric oxide, and leukocyte influx in the intestine, preventing injury.
- IL-17 was found in Paneth cells, with its intracellular pool decreasing upon TNF challenge, indicating rapid release.
Conclusions:
- IL-17 plays a critical role in mediating the detrimental inflammatory effects of TNF.
- Paneth cells are a novel source of IL-17 involved in acute inflammatory responses.
- Local mucosal innate immune responses, like IL-17 release, can amplify systemic inflammation.
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