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* Department of Pathobiology, School of Veterinary Medicine,
Abramson Family Cancer Research Institute and Department of Pathology and Laboratory Medicine, and
Division of Gastroenterology, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
Department of Inflammation Research, Amgen, Thousand Oaks, CA 91320;
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Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan, and PRESTO, Japan Science and Technology Agency, Honcho Kawaguchi, Saitama, Japan;
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Veterinary Clinical Studies, Easter Bush Veterinary Centre, University of Edinburgh, Easter Bush, Roslin, Midlothian, Scotland, United Kingdom; and
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Department of Molecular Biology, Genentech, South San Francisco, CA 94080
Although previous studies have investigated the role of IL-27/WSX-1 interactions in the regulation of Th1 responses, little is known about their role in regulating Th2-type responses. Studies presented in this work identify a direct role for IL-27/WSX-1 interactions in the negative regulation of type 2 responses independent of effects on type 1 cytokines. WSX-1–/– mice infected with the gastrointestinal helminth Trichuris muris displayed accelerated expulsion of parasites and the development of exaggerated goblet cell hyperplasia and mastocytosis in the gut due to increased production of Th2 cytokines. Enhanced mast cell activity in the absence of WSX-1 was consistent with the ability of wild-type mast cells to express this receptor. In addition, IL-27 directly suppressed CD4+ T cell proliferation and Th2 cytokine production. Together, these studies identify a novel role for IL-27/WSX-1 in limiting innate and adaptive components of type 2 immunity at mucosal sites.
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