{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:28:50Z","timestamp":1792740530669,"version":"4.5.0"},"reference-count":98,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2003,10,1]],"date-time":"2003-10-01T00:00:00Z","timestamp":1064966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>T helper 1 responses are typically proinflammatory, while Th2 responses have been considered regulatory. Interestingly, Th2 responses characterize a number of pulmonary diseases, many of which terminate in tissue remodeling and fibrosis. We developed a mouse model using Schistosoma mansoni eggs and cytokine-deficient mice to induce highly polarized Th1- or Th2-type inflammation in the lung. In this study, we examined the pathology and cytokine profiles in Th1- and Th2-polarized environments and used oligonucleotide microarray analysis to decipher the genes responsible for these effects. We further elaborated on the results using IL-10- and IL-13-deficient mice because these cytokines are believed to be the central regulators of Th2-associated pathology. We found that the Th1-polarized mice developed small granulomas with less fibrosis while expressing genes characteristic of tissue damage. Th2-polarized mice, in contrast, formed large granulomas with massive collagen deposition and up-regulated genes associated with wound healing, specifically, arginase, collagens, matrix metalloproteinases (MMPs), and tissue inhibitors of MMP. In addition, several members of the chitinase-like family were up-regulated in the lung following egg challenge. We also developed a method of defining the net collagen deposition using the expression profiles of several collagen, MMP, and tissue inhibitors of MMP genes. We found that Th1-polarized mice did not elaborate collagens or MMPs and therefore did not have a significant capacity for repair in this model. Thus, Th1-mediated inflammation is characterized by tissue damage, while Th2 directs wound healing and fibrosis.<\/jats:p>","DOI":"10.4049\/jimmunol.171.7.3655","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T23:19:35Z","timestamp":1398035975000},"page":"3655-3667","source":"Crossref","is-referenced-by-count":205,"title":["Global Gene Expression Profiles During Acute Pathogen-Induced Pulmonary Inflammation Reveal Divergent Roles for Th1 and Th2 Responses in Tissue Repair"],"prefix":"10.1093","volume":"171","author":[{"given":"Netanya G","family":"Sandler","sequence":"first","affiliation":[{"name":"Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M","family":"Mentink-Kane","sequence":"additional","affiliation":[{"name":"Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen W","family":"Cheever","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute , Rockville, MD 20852"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A","family":"Wynn","sequence":"additional","affiliation":[{"name":"Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,10,1]]},"reference":[{"key":"2026020211062531000_R1","first-page":"646","volume-title":"Am. J. Respir. Crit. Care Med.","year":"2000"},{"key":"2026020211062531000_R2","first-page":"251","volume-title":"Eur. Respir. J.","year":"1999"},{"key":"2026020211062531000_R3","first-page":"255","volume-title":"Curr. Opin. Pulm. Med.","year":"2001"},{"key":"2026020211062531000_R4","first-page":"629","volume-title":"Int. J. Radiat. Biol.","year":"1999"},{"key":"2026020211062531000_R5"},{"key":"2026020211062531000_R6","first-page":"298","volume-title":"N. Engl. J. Med.","year":"1992"},{"key":"2026020211062531000_R7","first-page":"1737","volume-title":"J. Exp. Med.","year":"1997"},{"key":"2026020211062531000_R8","first-page":"313","volume-title":"J. Allergy Clin. Immunol.","year":"1993"},{"key":"2026020211062531000_R9","first-page":"1430","volume-title":"J. Immunol.","year":"1993"},{"key":"2026020211062531000_R10","first-page":"900","volume-title":"J. Immunol.","year":"1992"},{"key":"2026020211062531000_R11","first-page":"1551","volume-title":"J. Exp. Med.","year":"1994"},{"key":"2026020211062531000_R12","first-page":"5190","volume-title":"J. Immunol.","year":"1994"},{"key":"2026020211062531000_R13","first-page":"6115","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1993"},{"key":"2026020211062531000_R14","first-page":"1","volume-title":"Adv. Immunol.","year":"1994"},{"key":"2026020211062531000_R15","first-page":"5014","volume-title":"J. Immunol.","year":"1997"},{"key":"2026020211062531000_R16","first-page":"927","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020211062531000_R17","first-page":"787","volume-title":"Nature","year":"1996"},{"key":"2026020211062531000_R18","first-page":"6755","volume-title":"Infect. Immun.","year":"2001"},{"key":"2026020211062531000_R19","first-page":"165","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020211062531000_R20","first-page":"2953","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020211062531000_R21","first-page":"2205","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020211062531000_R22","first-page":"723","volume-title":"Am. J. Respir. Crit. Care Med.","year":"2000"},{"key":"2026020211062531000_R23","first-page":"433","volume-title":"Int. J. Biochem. Cell Biol.","year":"1998"},{"key":"2026020211062531000_R24","first-page":"4235","volume-title":"Nucleic Acids Res.","year":"1997"},{"key":"2026020211062531000_R25","first-page":"319","volume-title":"Parasite Immunol.","year":"1999"},{"key":"2026020211062531000_R26","first-page":"425","volume-title":"Parasite Immunol.","year":"2000"},{"key":"2026020211062531000_R27","first-page":"2545","volume-title":"FASEB J.","year":"2001"},{"key":"2026020211062531000_R28","first-page":"284","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020211062531000_R29","first-page":"798","volume-title":"J. Immunol.","year":"1996"},{"key":"2026020211062531000_R30","first-page":"4045","volume-title":"J. Immunol.","year":"1996"},{"key":"2026020211062531000_R31","first-page":"4875","volume-title":"Mol. Cell. Biol.","year":"1993"},{"key":"2026020211062531000_R32","first-page":"9407","volume-title":"J. Biol. Chem.","year":"1995"},{"key":"2026020211062531000_R33","first-page":"436","volume-title":"Dev. Biol.","year":"1995"},{"key":"2026020211062531000_R34","first-page":"112","volume-title":"Nat. Rev. Mol. Cell Biol.","year":"2002"},{"key":"2026020211062531000_R35","first-page":"3350","volume-title":"Blood","year":"2002"},{"key":"2026020211062531000_R36","first-page":"1840","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020211062531000_R37","first-page":"41","volume-title":"Paediatr. Respir. Rev.","year":"2002"},{"key":"2026020211062531000_R38","first-page":"5739","volume-title":"J. Biol. Chem.","year":"2000"},{"key":"2026020211062531000_R39","first-page":"67","volume-title":"Curr. Opin. Allergy Clin. Immunol.","year":"2001"},{"key":"2026020211062531000_R40","first-page":"107","volume-title":"Int. J. Biochem. Cell Biol.","year":"1997"},{"key":"2026020211062531000_R41","first-page":"9","volume-title":"Cell Struct. Funct.","year":"2002"},{"key":"2026020211062531000_R42","first-page":"611","volume-title":"Am. J. Pathol.","year":"1998"},{"key":"2026020211062531000_R43","first-page":"783","volume-title":"J. Allergy Clin. Immunol.","year":"1998"},{"key":"2026020211062531000_R44","first-page":"160","volume-title":"Immunol. Cell Biol.","year":"2001"},{"key":"2026020211062531000_R45","first-page":"21","volume-title":"Connect. Tissue Res.","year":"1977"},{"key":"2026020211062531000_R46","first-page":"257","volume-title":"Connect. Tissue Res.","year":"1986"},{"key":"2026020211062531000_R47","first-page":"145","volume-title":"Matrix Biol.","year":"1998"},{"key":"2026020211062531000_R48","first-page":"799","volume-title":"Histochem. J.","year":"1998"},{"key":"2026020211062531000_R49","first-page":"89","volume-title":"Matrix Biol.","year":"2002"},{"key":"2026020211062531000_R50","first-page":"301","volume-title":"Exp. Biol. Med.","year":"2002"},{"key":"2026020211062531000_R51","first-page":"2688","volume-title":"J. Immunol.","year":"1995"},{"key":"2026020211062531000_R52","first-page":"899","volume-title":"Eur. Respir. J.","year":"1996"},{"key":"2026020211062531000_R53","first-page":"845","volume-title":"Am. J. Respir. Crit. Care Med.","year":"1997"},{"key":"2026020211062531000_R54","first-page":"520","volume-title":"Lancet","year":"1989"},{"key":"2026020211062531000_R55","first-page":"4379","volume-title":"J. Immunol.","year":"1995"},{"key":"2026020211062531000_R56","first-page":"688","volume-title":"Blood","year":"2001"},{"key":"2026020211062531000_R57","first-page":"519","volume-title":"Am. J. Respir. Cell Mol. Biol.","year":"1997"},{"key":"2026020211062531000_R58","first-page":"525","volume-title":"Am. J. Pathol.","year":"2000"},{"key":"2026020211062531000_R59","first-page":"517","volume-title":"J. Cell Biol.","year":"1999"},{"key":"2026020211062531000_R60","first-page":"3942","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1996"},{"key":"2026020211062531000_R61","first-page":"2139","volume-title":"Am. J. Pathol.","year":"2001"},{"key":"2026020211062531000_R62","first-page":"1338","volume-title":"Endocrinology","year":"1998"},{"key":"2026020211062531000_R63","first-page":"225","volume-title":"Matrix Biol.","year":"1999"},{"key":"2026020211062531000_R64","first-page":"276","volume-title":"Curr. Eye Res.","year":"1998"},{"key":"2026020211062531000_R65","first-page":"2154","volume-title":"Invest. Ophthalmol. Visual Sci.","year":"2000"},{"key":"2026020211062531000_R66","first-page":"48","volume-title":"J. Hepatol.","year":"1999"},{"key":"2026020211062531000_R67","first-page":"1081","volume-title":"J. Clin. Invest.","year":"2000"},{"key":"2026020211062531000_R68","first-page":"988","volume-title":"J. Pharmacol. Exp. Ther.","year":"2000"},{"key":"2026020211062531000_R69","first-page":"150","volume-title":"Ann. Rheum. Dis.","year":"2001"},{"key":"2026020211062531000_R70","first-page":"585","volume-title":"J. Leukocyte Biol.","year":"2001"},{"key":"2026020211062531000_R71","first-page":"809","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2026020211062531000_R72","first-page":"303","volume-title":"Oncol. Res.","year":"1996"},{"key":"2026020211062531000_R73","first-page":"189","volume-title":"Clin. Cancer Res.","year":"1999"},{"key":"2026020211062531000_R74","first-page":"226","volume-title":"Biochim. Biophys. Acta","year":"1996"},{"key":"2026020211062531000_R75","first-page":"1355","volume-title":"Am. J. Respir. Crit. Care Med.","year":"2000"},{"key":"2026020211062531000_R76","first-page":"101","volume-title":"Br. J. Rheumatol.","year":"1995"},{"key":"2026020211062531000_R77","first-page":"295","volume-title":"Eur. J. Clin. Invest.","year":"2002"},{"key":"2026020211062531000_R78","first-page":"821","volume-title":"Gastroenterology","year":"1996"},{"key":"2026020211062531000_R79","first-page":"826","volume-title":"Circulation","year":"2001"},{"key":"2026020211062531000_R80","first-page":"1478","volume-title":"Chest","year":"2002"},{"key":"2026020211062531000_R81","first-page":"227","volume-title":"Intervirology","year":"2001"},{"key":"2026020211062531000_R82","first-page":"202","volume-title":"J. Lab. Clin. Med.","year":"2002"},{"key":"2026020211062531000_R83","first-page":"1101","volume-title":"Eur. J. Immunol.","year":"1995"},{"key":"2026020211062531000_R84","first-page":"3771","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020211062531000_R85","first-page":"597","volume-title":"J. Leukocyte Biol.","year":"2002"},{"key":"2026020211062531000_R86","first-page":"6533","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020211062531000_R87","first-page":"25","volume-title":"J. Surg. Res.","year":"1996"},{"key":"2026020211062531000_R88","first-page":"1","volume-title":"Toxicology","year":"2000"},{"key":"2026020211062531000_R89","first-page":"997","volume-title":"Circulation","year":"1997"},{"key":"2026020211062531000_R90","first-page":"17497","volume-title":"J. Biol. Chem.","year":"2001"},{"key":"2026020211062531000_R91","first-page":"838","volume-title":"FASEB J.","year":"1996"},{"key":"2026020211062531000_R92","first-page":"6770","volume-title":"J. Biol. Chem.","year":"2001"},{"key":"2026020211062531000_R93","first-page":"323","volume-title":"Am. J. Pathol.","year":"2001"},{"key":"2026020211062531000_R94","first-page":"7","volume-title":"BMC Immunol.","year":"2002"},{"key":"2026020211062531000_R95","first-page":"173","volume-title":"Immunol. Lett.","year":"2003"},{"key":"2026020211062531000_R96","first-page":"257","volume-title":"J. Cell. Biochem.","year":"1997"},{"key":"2026020211062531000_R97","first-page":"41969","volume-title":"J. Biol. Chem.","year":"2001"},{"key":"2026020211062531000_R98","first-page":"2283","volume-title":"J. Immunol.","year":"1992"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/171\/7\/3655\/62590068\/3655.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/171\/7\/3655\/62590068\/3655.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T16:06:32Z","timestamp":1770048392000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/171\/7\/3655\/8031326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10,1]]},"references-count":98,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2003,10,1]]},"published-print":{"date-parts":[[2003,10,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.171.7.3655","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2003,10]]},"published":{"date-parts":[[2003,10,1]]}}}