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Mediators of Inflammation
Volume 2016 (2016), Article ID 5637685, 12 pages
Research Article

Exaggerated IL-15 and Altered Expression of foxp3+ Cell-Derived Cytokines Contribute to Enhanced Colitis in Nlrp3−/− Mice

1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada T2N 4N1
2Department of Microbiology, Immunology & Infectious Diseases, University of Calgary, Calgary, AB, Canada T2N 4N1
3Department of Medicine, University of Calgary, Calgary, AB, Canada T2N 4N1
4Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, AB, Canada T2N 4N1

Received 1 April 2016; Accepted 28 July 2016

Academic Editor: Ronald Gladue

Copyright © 2016 Simon A. Hirota et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The pathogenesis of Crohn’s disease (CD) involves defects in the innate immune system, impairing responses to microbes. Studies have revealed that mutations NLRP3 are associated with CD. We reported previously that Nlrp3−/− mice were more susceptible to colitis and exhibited reduced colonic IL-10 expression. In the current study, we sought to determine how the loss of NLRP3 might be altering the function of regulatory T cells, a major source of IL-10. Colitis was induced in wild-type (WT) and Nlrp3−/− mice by treatment with dextran sulphate sodium (DSS). Lamina propria (LP) cells were assessed by flow cytometry and cytokine expression was assessed. DSS-treated Nlrp3−/− mice exhibited increased numbers of colonic foxp3+ T cells that expressed significantly lower levels of IL-10 but increased IL-17. This was associated with increased expression of colonic IL-15 and increased surface expression of IL-15 on LP dendritic cells. Neutralizing IL-15 in Nlrp3−/− mice attenuated the severity of colitis, decreased the number of colonic foxp3+ cells, and reduced the colonic expression of IL-12p40 and IL-17. These data suggest that the NLRP3 inflammasome can regulate intestinal inflammation through noncanonical mechanisms, providing additional insight as to how NLRP3 variants may contribute to the pathogenesis of CD.