Journal article
Role of T Cell TGF-β Signaling in Intestinal Cytokine Responses and Helminthic Immune Modulation
European journal of immunology, Vol.39(7), pp.1870-1878
07/2009
DOI: 10.1002/eji.200838956
PMCID: PMC2882993
PMID: 19544487
Abstract
Colonization with helminthic parasites induces mucosal regulatory cytokines, like IL-10 or TGF-β that are important in suppressing colitis. Helminths induce mucosal T cell IL-10 secretion and regulate lamina propria mononuclear cell Th1 cytokine generation in an IL-10 dependent manner in wild-type mice. Helminths also stimulate mucosal TGF-β release. As TGF-β exerts major regulatory effects on T lymphocytes, we investigated the role of T lymphocyte TGF-β signaling in helminthic modulation of intestinal immunity. T cell TGF-β signaling is interrupted in TGF-βRII DN mice by T cell-specific over-expression of a dominant negative TGF-β receptor II. We studied lamina propria mononuclear cell responses in wild-type and TGF-βRII DN mice that were uninfected or colonized with the nematode,
Heligmosomoides polygyrus
. Our results indicate an essential role of T cell TGF-β signaling in limiting mucosal Th1 and Th2 responses. Furthermore, we demonstrate that helminthic induction of intestinal T cell IL-10 secretion requires intact T cell TGF-β signaling pathway. Helminths fail to curtail robust, dysregulated intestinal Th1 cytokine production and chronic colitis in TGF-βRII DN mice. Thus, T cell TGF-β signaling is essential for helminthic stimulation of mucosal IL-10 production, helminthic modulation of intestinal interferon-γ generation and
H. polygyrus
-mediated suppression of chronic colitis.
Details
- Title: Subtitle
- Role of T Cell TGF-β Signaling in Intestinal Cytokine Responses and Helminthic Immune Modulation
- Creators
- M. Nedim Ince - Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA, U.S.ADavid E Elliott - Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA, U.S.ATommy Setiawan - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tufts New England Medical Center, Boston, MA, U.S.AAhmed Metwali - Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA, U.S.AArthur Blum - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tufts New England Medical Center, Boston, MA, U.S.AHung-lin Chen - Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA, U.S.AJoseph F Urban - U.S. Department of Agriculture, Agricultural Research Service, Diet, Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, Beltsville, MD, U.S.ARichard A Flavell - Section of Immunobiology, Yale University School of Medicine, New Haven, CT, U.S.AJoel V Weinstock - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tufts New England Medical Center, Boston, MA, U.S.A
- Resource Type
- Journal article
- Publication Details
- European journal of immunology, Vol.39(7), pp.1870-1878
- DOI
- 10.1002/eji.200838956
- PMID
- 19544487
- PMCID
- PMC2882993
- ISSN
- 0014-2980
- eISSN
- 1521-4141
- Language
- English
- Date published
- 07/2009
- Academic Unit
- Gastroenterology and Hepatology; Internal Medicine
- Record Identifier
- 9984094618602771
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