{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:46:59Z","timestamp":1792572419478,"version":"4.5.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,9,14]]},"abstract":"<jats:p>\n                    Gastrointestinal (GI) nematode infections are an important public health and economic concern. Experimental studies have shown that resistance to infection requires CD4\n                    <jats:sup>+<\/jats:sup>\n                    T helper type 2 (Th2) cytokine responses characterized by the production of IL-4 and IL-13. However, despite &gt;30 years of research, it is unclear how the immune system mediates the expulsion of worms from the GI tract. Here, we demonstrate that a recently described intestinal goblet cell-specific protein, RELM\u03b2\/FIZZ2, is induced after exposure to three phylogenetically distinct GI nematode pathogens. Maximal expression of RELM\u03b2 was coincident with the production of Th2 cytokines and host protective immunity, whereas production of the Th1 cytokine, IFN-\u03b3, inhibited RELM\u03b2 expression and led to chronic infection. Furthermore, whereas induction of RELM\u03b2 was equivalent in nematode-infected wild-type and IL-4-deficient mice, IL-4 receptor-deficient mice showed minimal RELM\u03b2 induction and developed persistent infections, demonstrating a direct role for IL-13 in optimal expression of RELM\u03b2. Finally, we show that RELM\u03b2 binds to components of the nematode chemosensory apparatus and inhibits chemotaxic function of a parasitic nematode\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Together, these results suggest that intestinal goblet cell-derived RELM\u03b2 may be a novel Th2 cytokine-induced immune-effector molecule in resistance to GI nematode infection.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0404034101","type":"journal-article","created":{"date-parts":[[2004,8,30]],"date-time":"2004-08-30T20:14:24Z","timestamp":1093896864000},"page":"13596-13600","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":300,"title":["RELM\u03b2\/FIZZ2 is a goblet cell-specific immune-effector molecule in the gastrointestinal tract"],"prefix":"10.1073","volume":"101","author":[{"given":"David","family":"Artis","sequence":"first","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104; Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Divisions of Gastroenterology and Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104; Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei Lun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104; Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Divisions of Gastroenterology and Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104; Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue A.","family":"Keilbaugh","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104; Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Divisions of Gastroenterology and Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104; Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimian","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104; Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Divisions of Gastroenterology and Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104; Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Brenes","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104; Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Divisions of Gastroenterology and Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104; Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary P.","family":"Swain","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104; Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Divisions of Gastroenterology and Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104; Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela A.","family":"Knight","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104; Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Divisions of Gastroenterology and Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104; Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah D.","family":"Donaldson","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104; Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Divisions of Gastroenterology and Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104; Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell A.","family":"Lazar","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104; Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Divisions of Gastroenterology and Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104; Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh R. P.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104; Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Divisions of Gastroenterology and Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104; Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard A.","family":"Schad","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104; Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Divisions of Gastroenterology and Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104; Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104; Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Divisions of Gastroenterology and Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104; Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary D.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104; Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA 19104; Divisions of Gastroenterology and Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Suite 600, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104; Division of Veterinary Clinical Studies, University of Edinburgh, Easter Bush..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,8,30]]},"reference":[{"key":"e_1_3_2_1_2","unstructured":"World Health Organization. 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