The IL-27 Receptor (WSX-1) Is an Inhibitor of Innate and Adaptive Elements of Type 2 Immunity
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 typ...
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| Published in | The Journal of immunology (1950) Vol. 173; no. 9; pp. 5626 - 5634 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Am Assoc Immnol
01.11.2004
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| Subjects | |
| Online Access | Get full text |
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| Abstract | 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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| AbstractList | 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 super(-/-) 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 super(+) 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. Abstract 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. 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. |
| Author | Hunter, Christopher A Miller, Hugh R. P Mu, Sharon Huang, Elaine Summer, Shamin Koretzky, Gary Goldschmidt, Michael Covey, Todd M Yoshida, Hiroki Villarino, Alejandro He, Weimian de Sauvage, Fred Scott, Phillip Silverman, Michael Artis, David Saris, Christiaan J. M Wu, Gary D Thornton, Elizabeth M |
| Author_xml | – sequence: 1 fullname: Artis, David – sequence: 2 fullname: Villarino, Alejandro – sequence: 3 fullname: Silverman, Michael – sequence: 4 fullname: He, Weimian – sequence: 5 fullname: Thornton, Elizabeth M – sequence: 6 fullname: Mu, Sharon – sequence: 7 fullname: Summer, Shamin – sequence: 8 fullname: Covey, Todd M – sequence: 9 fullname: Huang, Elaine – sequence: 10 fullname: Yoshida, Hiroki – sequence: 11 fullname: Koretzky, Gary – sequence: 12 fullname: Goldschmidt, Michael – sequence: 13 fullname: Wu, Gary D – sequence: 14 fullname: de Sauvage, Fred – sequence: 15 fullname: Miller, Hugh R. P – sequence: 16 fullname: Saris, Christiaan J. M – sequence: 17 fullname: Scott, Phillip – sequence: 18 fullname: Hunter, Christopher A |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/15494513$$D View this record in MEDLINE/PubMed |
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| Snippet | 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... Abstract 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... |
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| SubjectTerms | Animals Cytokines - biosynthesis Down-Regulation - immunology Goblet Cells - immunology Goblet Cells - pathology Immunity, Innate - genetics Immunity, Mucosal - genetics Interferon-gamma - antagonists & inhibitors Interferon-gamma - biosynthesis Interleukins - biosynthesis Interleukins - genetics Interleukins - physiology Intestinal Diseases, Parasitic - genetics Intestinal Diseases, Parasitic - immunology Intestinal Diseases, Parasitic - pathology Mastocytosis - genetics Mastocytosis - immunology Mastocytosis - pathology Mice Mice, Inbred C57BL Mice, Knockout Receptors, Cytokine - deficiency Receptors, Cytokine - genetics Receptors, Cytokine - physiology RNA, Messenger - biosynthesis Suppressor Factors, Immunologic - deficiency Suppressor Factors, Immunologic - genetics Suppressor Factors, Immunologic - physiology Th2 Cells - immunology Th2 Cells - metabolism Th2 Cells - parasitology Trichuriasis - genetics Trichuriasis - immunology Trichuriasis - parasitology Trichuriasis - pathology Trichuris - growth & development Trichuris - immunology |
| Title | The IL-27 Receptor (WSX-1) Is an Inhibitor of Innate and Adaptive Elements of Type 2 Immunity |
| URI | http://www.jimmunol.org/cgi/content/abstract/173/9/5626 https://www.ncbi.nlm.nih.gov/pubmed/15494513 https://search.proquest.com/docview/18031093 https://search.proquest.com/docview/66994566 |
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