{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:10:39Z","timestamp":1791497439848,"version":"4.3.4"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":3014,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Immunoglobin G (IgG) 4-related sclerosing pancreatitis and cholangitis (autoimmune pancreato-cholangitis [AIPC]) are recently recognized disease entities characterized by high serum IgG4 concentrations and sclerosing inflammation with numerous IgG4-positive plasma cells, although the underlining immune mechanism remains only speculative. In this study, the immunopathogenesis of AIPC was examined with respect to the production of cytokines<\/jats:bold>\n                                 <jats:bold>\n                                    in situ\n                                 <\/jats:bold>\n                                 <jats:bold>and the possible involvement of regulatory T cells (Tregs) using fresh (5 cases) and formalin-fixed (28 cases) specimens of AIPC and related extra-pancreatobiliary lesions. Quantitative real-time polymerase chain reaction revealed that AIPC and extra-pancreatobiliary lesions had significantly higher ratios of interleukin (IL)-4\/interferon-\u03b3 (IFN-\u03b3) (45.8-fold), IL-5\/IFN-\u03b3 (18.7-fold), IL-13\/interferon (IFN)-\u03b3 (20.7-fold), IL-10\/CD4 (45.3-fold), and tumor growth factor (TGF)-\u03b2\/CD4 (39.4-fold) than did primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Lymphocytes with signals for IL-4 and IL-10 were frequently found in AIPC by<\/jats:bold>\n                                 <jats:bold>\n                                    in situ\n                                 <\/jats:bold>\n                                 <jats:bold>hybridization. The expression of Foxp3 messenger RNA, a transcription factor specific for naturally arising CD4+CD25+ Tregs, was significantly increased in AIPC and extra-pancreatobiliary lesions in comparison to PSC and PBC (36.4-fold). Immunohistochemically, CD4+CD25+Foxp3+ cells were frequently found in AIPC, while few were found in PSC and other disease controls. Taken together, AIPC could be characterized by the over-production of T helper (Th) 2 and regulatory cytokines. Tregs might be involved in the<\/jats:bold>\n                                 <jats:bold>\n                                    in situ\n                                 <\/jats:bold>\n                                 <jats:bold>production of IL-10 and TGF-\u03b2, which could be followed by IgG4 class switching and fibroplasia.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>AIPC is a unique inflammatory disorder characterized by an immune reaction predominantly mediated by Th2 cells and Tregs. (Hepatology 2007.)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.21697","type":"journal-article","created":{"date-parts":[[2007,5,24]],"date-time":"2007-05-24T00:22:58Z","timestamp":1179966178000},"page":"1538-1546","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":584,"title":["Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis"],"prefix":"10.1097","volume":"45","author":[{"given":"Yoh","family":"Zen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiko","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Kawano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Takahira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuni","family":"Nakanuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-26-20241201","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1056\/NEJM200103083441005","article-title":"High serum IgG4 concentrations in patients with sclerosing pancreatitis.","volume":"344","author":"Hamano","year":"2001","journal-title":"N Engl J Med"},{"key":"R2-26-20241201","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1136\/gut.52.5.683","article-title":"Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis.","volume":"52","author":"Kamisawa","year":"2003","journal-title":"Gut"},{"key":"R3-26-20241201","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/S0140-6736(02)08359-9","article-title":"Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis.","volume":"359","author":"Hamano","year":"2002","journal-title":"Lancet"},{"key":"R4-26-20241201","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1097\/01.pas.0000136449.37936.6c","article-title":"IgG4related sclerosing cholangitis with and without hepatic inflammatory pseudotumor, and sclerosing pancreatitisassociated sclerosing cholangitis: do they 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