{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T10:32:26Z","timestamp":1761561146921,"version":"3.33.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2007,4,5]],"date-time":"2007-04-05T00:00:00Z","timestamp":1175731200000},"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":[[2007,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Excessive scarring or fibrosis is a common feature of a wide spectrum of diseases characterized by an exaggerated Th2 response. The TLR\/IL-1 receptor (IL-1R)-related protein ST2 is expressed in a membrane-bound form selectively by Th2 cells and was shown to be indispensable for some in vivo Th2 responses. ST2 was also found to block TLR signaling. We addressed the impact of the ST2 pathway on fibrogenesis using a mouse model of hepatic injury and fibrosis induced by carbon tetrachloride (CCl4). We showed that cytokine production by intrahepatic lymphocytes from CCl4-injured liver is abrogated in the absence of TLR-4. Interfering with the ST2 pathway using an ST2-Fc fusion protein accelerated and enhanced hepatic fibrosis, paralleled by the increasing ex vivo secretion of Th2 cytokines IL-4, -5, -10, and -13 by intrahepatic lymphocytes of ST2-Fc-treated, CCl4-gavaged mice. Absence of IL-4\/13 signaling in IL-4R\u03b1-deficient mice obliterated this ST2-Fc effect on fibrogenesis. Moreover, depletion of CD4+ T cells abrogated ST2-Fc-enhanced Th2 cytokines and accelerated fibrosis. Thus, ST2-Fc caused overproduction of Th2 cytokines by intrahepatic CD4+ T cells, possibly by modifying TLR-4 signaling in injured liver. This ST2-Fc-driven Th2 response exacerbated CCl4-induced hepatic fibrosis.<\/jats:p>","DOI":"10.1189\/jlb.1006625","type":"journal-article","created":{"date-parts":[[2007,4,6]],"date-time":"2007-04-06T01:03:45Z","timestamp":1175821425000},"page":"124-132","source":"Crossref","is-referenced-by-count":22,"title":["Recombinant ST2 boosts hepatic Th2 response in vivo"],"prefix":"10.1093","volume":"82","author":[{"given":"Aldo","family":"Amatucci","sequence":"first","affiliation":[{"name":"Biogen Idec , Cambridge, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Novobrantseva","sequence":"additional","affiliation":[{"name":"Biogen Idec , Cambridge, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Gilbride","sequence":"additional","affiliation":[{"name":"Biogen Idec , Cambridge, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margot","family":"Brickelmaier","sequence":"additional","affiliation":[{"name":"Biogen Idec , Cambridge, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Hochman","sequence":"additional","affiliation":[{"name":"Biogen Idec , Cambridge, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Ibraghimov","sequence":"additional","affiliation":[{"name":"Biogen Idec , Cambridge, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,4,5]]},"reference":[{"key":"2023033006513525400_","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1002\/j.1460-2075.1994.tb06367.x","article-title":"Alternative promoter usage of the Fos-responsive gene Fit-1 generates mRNA isoforms coding for either secreted or membrane-bound proteins related to the IL-1 receptor","volume":"13","author":"Bergers","year":"1994","journal-title":"EMBO J."},{"key":"2023033006513525400_","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1006\/cyto.1998.0359","article-title":"Divergent effects of LPS on expression of IL-1 receptor family members in mononuclear phagocytes in vitro and in vivo","volume":"10","author":"Saccani","year":"1998","journal-title":"Cytokine"},{"key":"2023033006513525400_","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S0006-291X(02)02578-0","article-title":"ST2 protein induced by inflammatory stimuli can modulate acute lung inflammation","volume":"299","author":"Oshikawa","year":"2002","journal-title":"Biochem. 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