{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:35:14Z","timestamp":1791398114262,"version":"4.3.3"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T00:00:00Z","timestamp":1241136000000},"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":[[2009,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Thymic stromal lymphopoietin was recently identified as a master switch for the development of allergen-driven Th2 responses. However, the role of thymic stromal lymphopoietin (TSLP) in the development of helminth-induced Th2 responses is unclear. Here, using TSLPR\u2212\/\u2212 mice, we show that while TSLPR signaling participates in the development of Schistosoma mansoni egg-induced CD4+ Th2 responses, it plays only a transient role in the development of Th2-dependent pathology in the lung, liver, and intestine. Studies conducted in a pulmonary granuloma model showed that while a reduction in IL-4\/IL-13-dependent granulomatous inflammation and tissue eosinophilia was observed in TSLPR\u2212\/\u2212 mice undergoing a primary response, lesion formation was not affected during a secondary granulomatous response, even though IL-5 and IL-13 were modestly reduced in the knockout mice. To evaluate the importance of TSLPR signaling in the development of a chronic Th2-dependent response, TSLPR\u2212\/\u2212 mice were also infected with S. mansoni cercariae. Here, the only significant difference noted in TSLPR\u2212\/\u2212 mice was a modest decrease in liver fibrosis in acutely infected animals. The transient decrease in fibrosis was associated with increased production of the antifibrotic cytokine IFN-\u03b3 and decreased production of the profibrotic cytokine IL-13. Although the altered cytokine response persisted in chronically infected TSLPR\u2212\/\u2212 mice, it failed to reduce granuloma formation or fibrosis, confirming that TSLPR signaling plays a limited role in the development of chronic Th2-dependent pathology. Collectively, these findings suggest that while TSLPR signaling serves a key role in allergen-driven Th2 responses, it exerts minor regulatory activity during this chronic helminth infection.<\/jats:p>","DOI":"10.4049\/jimmunol.0900181","type":"journal-article","created":{"date-parts":[[2009,5,4]],"date-time":"2009-05-04T16:48:20Z","timestamp":1241455700000},"page":"6452-6459","source":"Crossref","is-referenced-by-count":54,"title":["Regulation of Helminth-Induced Th2 Responses by Thymic Stromal Lymphopoietin"],"prefix":"10.1093","volume":"182","author":[{"given":"Thirumalai R","family":"Ramalingam","sequence":"first","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T","family":"Pesce","sequence":"additional","affiliation":[{"name":"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":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Madala","sequence":"additional","affiliation":[{"name":"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":"Michael R","family":"Comeau","sequence":"additional","affiliation":[{"name":"Department of Inflammation , Amgen, Seattle, WA 98119"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven F","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Immunology Program, Benaroya Research Institute , Seattle, WA 98101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A","family":"Wynn","sequence":"additional","affiliation":[{"name":"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":[[2009,5,15]]},"reference":[{"key":"2026012806320621900_R1","first-page":"677","article-title":"Thymic stromal lymphopoietin: a cytokine that promotes the development of IgM+ B cells in vitro and signals via a novel mechanism.","volume-title":"J. Immunol.","year":"1999"},{"key":"2026012806320621900_R2","first-page":"10","article-title":"Characterization of thymic stromal-derived lymphopoietin (TSLP) in murine B cell development in vitro.","volume-title":"Eur. J. Immunol.","year":"1996"},{"key":"2026012806320621900_R3","first-page":"671","article-title":"Molecular cloning and biological characterization of a novel murine lymphoid growth factor.","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2026012806320621900_R4","first-page":"11875","article-title":"TSLP acts on infiltrating effector T cells to drive allergic skin inflammation.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2008"},{"key":"2026012806320621900_R5","first-page":"269","article-title":"Thymic stromal lymphopoietin: master switch for allergic inflammation.","volume-title":"J. Exp. Med.","year":"2006"},{"key":"2026012806320621900_R6","first-page":"202","article-title":"Local blockade of TSLP receptor alleviated allergic disease by regulating airway dendritic cells.","volume-title":"Clin. Immunol.","year":"2008"},{"key":"2026012806320621900_R7","first-page":"325","article-title":"Human thymic stromal lymphopoietin: a novel epithelial cell-derived cytokine and a potential key player in the induction of allergic inflammation.","volume-title":"Springer Semin. Immunopathol.","year":"2004"},{"key":"2026012806320621900_R8","first-page":"709","article-title":"Thymic stromal lymphopoietin in normal and pathogenic T cell development and function.","volume-title":"Nat. Immunol.","year":"2006"},{"key":"2026012806320621900_R9","first-page":"59","article-title":"Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin.","volume-title":"Nat. Immunol.","year":"2000"},{"key":"2026012806320621900_R10","first-page":"659","article-title":"Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: formation of a functional heteromeric complex requires interleukin 7 receptor.","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2026012806320621900_R11","first-page":"336","article-title":"Human thymic stromal lymphopoietin preferentially stimulates myeloid cells.","volume-title":"J. Immunol.","year":"2001"},{"key":"2026012806320621900_R12","first-page":"159","article-title":"A role for thymic stromal lymphopoietin in CD4+ T cell development.","volume-title":"J. Exp. Med.","year":"2004"},{"key":"2026012806320621900_R13","first-page":"426","article-title":"Human thymic stromal lymphopoietin promotes dendritic cell-mediated CD4+ T cell homeostatic expansion.","volume-title":"Nat. Immunol","year":"2004"},{"key":"2026012806320621900_R14","first-page":"673","article-title":"Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP.","volume-title":"Nat. Immunol.","year":"2002"},{"key":"2026012806320621900_R15","first-page":"552","article-title":"Epithelial-cell-intrinsic IKK-\u03b2 expression regulates intestinal immune homeostasis.","volume-title":"Nature","year":"2007"},{"key":"2026012806320621900_R16","first-page":"310","article-title":"A mechanism for the initiation of allergen-induced T helper type 2 responses.","volume-title":"Nat. Immunol.","year":"2008"},{"key":"2026012806320621900_R17","first-page":"1213","article-title":"TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand.","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2026012806320621900_R18","first-page":"1837","article-title":"IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells.","volume-title":"J. Exp. Med.","year":"2007"},{"key":"2026012806320621900_R19","first-page":"1059","article-title":"Human dendritic cells activated by TSLP and CD40L induce proallergic cytotoxic T cells.","volume-title":"J. Exp. Med.","year":"2003"},{"key":"2026012806320621900_R20","first-page":"4749","article-title":"Human TSLP promotes CD40 ligand-induced IL-12 production by myeloid dendritic cells but maintains their Th2 priming potential.","volume-title":"Blood","year":"2005"},{"key":"2026012806320621900_R21","first-page":"827","article-title":"Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells.","volume-title":"Immunity","year":"2006"},{"key":"2026012806320621900_R22","first-page":"1396","article-title":"Induction of IL-4 expression in CD4+ T cells by thymic stromal lymphopoietin.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012806320621900_R23","first-page":"253","article-title":"Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells.","volume-title":"J. Exp. Med.","year":"2007"},{"key":"2026012806320621900_R24","first-page":"1080","article-title":"TLR3- and Th2 cytokine-dependent production of thymic stromal lymphopoietin in human airway epithelial cells.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012806320621900_R25","first-page":"8183","article-title":"Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity.","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012806320621900_R26","first-page":"829","article-title":"A role for TSLP in the development of inflammation in an asthma model.","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2026012806320621900_R27","first-page":"1047","article-title":"Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice.","volume-title":"Nat. Immunol.","year":"2005"},{"key":"2026012806320621900_R28","first-page":"4311","article-title":"Intradermal administration of thymic stromal lymphopoietin induces a T cell- and eosinophil-dependent systemic Th2 inflammatory response.","volume-title":"J. Immunol.","year":"2008"},{"key":"2026012806320621900_R29","first-page":"6557","article-title":"Reversal of thymic stromal lymphopoietin-induced airway inflammation through inhibition of Th2 responses.","volume-title":"J. Immunol.","year":"2008"},{"key":"2026012806320621900_R30","first-page":"51","article-title":"Interleukin-13: a key mediator in resistance to gastrointestinal-dwelling nematode parasites.","volume-title":"Clin. Rev. Allergy Immunol.","year":"2004"},{"key":"2026012806320621900_R31","first-page":"499","article-title":"The immunobiology of schistosomiasis.","volume-title":"Nat. Rev. Immunol.","year":"2002"},{"key":"2026012806320621900_R32","first-page":"465","article-title":"Immunopathology of schistosomiasis mansoni in mice and men.","volume-title":"Immunol. Today","year":"2000"},{"key":"2026012806320621900_R33","first-page":"753","article-title":"Anti-IL-4 treatment of Schistosoma mansoni-infected mice inhibits development of T cells and non-B, non-T cells expressing Th2 cytokines while decreasing egg-induced hepatic fibrosis.","volume-title":"J. Immunol.","year":"1994"},{"key":"2026012806320621900_R34","first-page":"777","article-title":"An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response.","volume-title":"J. Clin. Invest.","year":"1999"},{"key":"2026012806320621900_R35","first-page":"2044","article-title":"The IL-21 receptor augments Th2 effector function and alternative macrophage activation.","volume-title":"J. Clin. Invest.","year":"2006"},{"key":"2026012806320621900_R36","first-page":"1471","article-title":"Interleukin-5 (IL-5) augments the progression of liver fibrosis by regulating IL-13 activity.","volume-title":"Infect. Immun.","year":"2006"},{"key":"2026012806320621900_R37","first-page":"288","article-title":"Th2 cytokines are associated with persistent hepatic fibrosis in human Schistosoma japonicum infection.","volume-title":"J. Infect. Dis.","year":"2007"},{"key":"2026012806320621900_R38","first-page":"3391","article-title":"Association of type 2 cytokines with hepatic fibrosis in human Schistosoma mansoni infection.","volume-title":"Infect. Immun.","year":"2004"},{"key":"2026012806320621900_R39","first-page":"2585","article-title":"Schistosome infection of transgenic mice defines distinct and contrasting pathogenic roles for IL-4 and IL-13: IL-13 is a profibrotic agent.","volume-title":"J. Immunol.","year":"2000"},{"key":"2026012806320621900_R40","first-page":"337","article-title":"Schistosome-infected IL-4 receptor knockout (KO) mice, in contrast to IL-4 KO mice, fail to develop granulomatous pathology while maintaining the same lymphokine expression profile.","volume-title":"J. Immunol.","year":"1999"},{"key":"2026012806320621900_R41","first-page":"25","article-title":"Unique functions of the type II interleukin 4 receptor identified in mice lacking the interleukin 13 receptor \u03b11 chain.","volume-title":"Nat. Immunol.","year":"2008"},{"key":"2026012806320621900_R42","first-page":"1430","article-title":"Analysis of cytokine mRNA expression during primary granuloma formation induced by eggs of Schistosoma mansoni.","volume-title":"J. Immunol.","year":"1993"},{"key":"2026012806320621900_R43","first-page":"425","article-title":"IL-13 effector functions.","volume-title":"Annu. Rev. Immunol.","year":"2003"},{"key":"2026012806320621900_R44","first-page":"583","article-title":"Fibrotic disease and the TH1\/TH2 paradigm.","volume-title":"Nat. Rev. Immunol.","year":"2004"},{"key":"2026012806320621900_R45","first-page":"594","article-title":"An IL-12-based vaccination method for preventing fibrosis induced by schistosome infection.","volume-title":"Nature","year":"1995"},{"key":"2026012806320621900_R46","first-page":"605","article-title":"TSLP: finally in the limelight.","volume-title":"Nat. Immunol.","year":"2002"},{"key":"2026012806320621900_R47","first-page":"541","article-title":"Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin.","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2026012806320621900_R48","first-page":"975","article-title":"Protective immune mechanisms in helminth infection.","volume-title":"Nat. Rev. Immunol.","year":"2007"},{"key":"2026012806320621900_R49","first-page":"1871","article-title":"Schistosoma mansoni egg-induced early IL-4 production is dependent upon IL-5 and eosinophils.","volume-title":"J. Exp. Med.","year":"1996"},{"key":"2026012806320621900_R50","first-page":"920","article-title":"IL-13 is a key regulatory cytokine for Th2 cell-mediated pulmonary granuloma formation and IgE responses induced by Schistosoma mansoni eggs.","volume-title":"J. Immunol.","year":"1999"},{"key":"2026012806320621900_R51","first-page":"1565","article-title":"Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2-mediated responses.","volume-title":"J. Exp. Med.","year":"1999"},{"key":"2026012806320621900_R52","first-page":"156","article-title":"Immunopathogenesis of schistosomiasis.","volume-title":"Immunol. Rev.","year":"2004"},{"key":"2026012806320621900_R53","first-page":"777","article-title":"IL-4 protects against TNF-\u03b1-mediated cachexia and death during acute schistosomiasis.","volume-title":"J. Immunol.","year":"1997"},{"key":"2026012806320621900_R54","first-page":"6406","article-title":"IL-10 and the dangers of immune polarization: excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis.","volume-title":"J. Immunol.","year":"2000"},{"key":"2026012806320621900_R55","first-page":"3920","article-title":"Severe CD4 T cell-mediated immunopathology in murine schistosomiasis is dependent on IL-12p40 and correlates with high levels of IL-17.","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012806320621900_R56","first-page":"273","article-title":"Studies of murine schistosomiasis reveal interleukin-13 blockade as a treatment for established and progressive liver fibrosis.","volume-title":"Hepatology","year":"2001"},{"key":"2026012806320621900_R57","first-page":"248","article-title":"The epithelium takes centre stage in asthma and atopic dermatitis.","volume-title":"Trends Immunol.","year":"2007"},{"key":"2026012806320621900_R58","first-page":"372","article-title":"Thymic stromal lymphopoietin: a potential therapeutic target for allergy and asthma.","volume-title":"Curr. Allergy Asthma Rep.","year":"2006"},{"key":"2026012806320621900_R59","first-page":"1105","article-title":"Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion.","volume-title":"J. Exp. Med.","year":"2006"},{"key":"2026012806320621900_R60","first-page":"3047","article-title":"Single cell analysis reveals that IL-4 receptor\/Stat6 signaling is not required for the in vivo or in vitro development of CD4+ lymphocytes with a Th2 cytokine profile.","volume-title":"J. Immunol.","year":"2000"},{"key":"2026012806320621900_R61","first-page":"843","article-title":"Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract.","volume-title":"J. Exp. Med.","year":"2006"},{"key":"2026012806320621900_R62","first-page":"2023","article-title":"IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo.","volume-title":"Blood","year":"2007"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/10\/6452\/62681639\/8986.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/10\/6452\/62681639\/8986.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:35:30Z","timestamp":1769600130000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/182\/10\/6452\/8007162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,5]]},"references-count":62,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2009,5,15]]},"published-print":{"date-parts":[[2009,5,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0900181","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,5]]},"published":{"date-parts":[[2009,5]]}}}