November 12, 2014
Notes: Seo, Yu Ri
Moon, Jong Ho
Choi, Hyun Jong
Kim, Dong Choon
Lee, Tae Hoon
Cho, Young Deok
J Gastroenterol Hepatol. 2013 Aug;28(8):1416-21. doi: 10.1111/jgh.12277.
Author Address: Digestive Disease Center and Research Institute, Department of Internal Medicine, Soon Chun Hyang University School of Medicine, Bucheon and Seoul, Korea.
Reference Type: Journal Article
Record Number: 5186Author: Sesti-Costa, R., Silva, G. K., Proenca-Modena, J. L., Carlos, D., Silva, M. L., Alves-Filho, J. C., Arruda, E., Liew, F. Y. and Silva, J. S.
Title: The IL-33/ST2 pathway controls coxsackievirus B5-induced experimental pancreatitis
Journal: J Immunol
Date: Jul 1
Short Title: The IL-33/ST2 pathway controls coxsackievirus B5-induced experimental pancreatitis
Alternate Journal: Journal of immunology
ISSN: 1550-6606 (Electronic)
Accession Number: 23733876
Disease Models, Animal
Interleukins/administration & dosage/biosynthesis/*physiology
Mice, Inbred BALB C
Abstract: Coxsackievirus B (CVB) is a common cause of acute and chronic infectious myocarditis and pancreatitis. Th1 cells producing IFN-gamma and TNF-alpha are important for CVB clearance, but they are also associated with the pathogenesis of inflammatory lesions, suggesting that the modulation of Th1 and Th2 balance is likely important in controlling CVB-induced pancreatitis. We investigated the role of IL-33, which is an important recently discovered cytokine for induction of Th2-associated responses, in experimental CVB5 infection. We found that mice deficient in IL-33R, T1/ST2, significantly developed more severe pancreatitis, had greater weight loss, and contained higher viral load compared with wild-type (WT) mice when infected with CVB5. Conversely, WT mice treated with rIL-33 developed significantly lower viral titers, and pancreatitis was attenuated. Mechanistic studies demonstrated that IL-33 enhances the degranulation and production of IFN-gamma and TNF-alpha by CD8(+) T and NK cells, which is associated with viral clearance. Furthermore, IL-33 triggers the production of IL-4 from mast cells, which results in enhanced differentiation of M2 macrophages and regulatory T cells, leading to the attenuation of inflammatory pancreatitis. Adoptively transferred mast cells or M2 macrophages reversed the heightened pancreatitis in the T1/ST2(-/-) mice. In contrast, inhibition of regulatory T cells exacerbated the disease in WT mice. Together, our findings reveal an unrecognized IL-33/ST2 functional pathway and a key mechanism for CVB5-induced pancreatitis. These data further suggest a novel approach in treating virus-induced pancreatitis, which is a major medical condition with unmet clinical needs.