{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:32:23Z","timestamp":1791063143276,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"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":[[2011,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The chemokine receptor CXCR3 is preferentially expressed by Th1 cells and critically involved in their recruitment to inflamed tissue. In a mouse model of immune-mediated liver injury inducible by Con A, we investigated the role of CXCR3 in acute IFN-\u03b3\u2013mediated hepatitis as well as in tolerance induction, which has been shown to depend on IL-10\u2013producing CD4+CD25+Foxp3+ regulatory T cells (Tregs). Induction of Con A hepatitis resulted in increased intrahepatic expression of the CXCR3 ligands CXCL9, CXCL10, and CXCL11. CXCR3\u2212\/\u2212 mice developed a more severe liver injury with higher plasma transaminase activities and a more pronounced Th1\/Th17 response compared with wild-type (wt) animals upon Con A injection. Moreover, CXCR3\u2212\/\u2212 mice did not establish tolerance upon Con A restimulation, although Tregs from CXCR3\u2212\/\u2212 mice were still suppressive in an in vitro suppression assay. Instead, Tregs failed to accumulate in livers of CXCR3\u2212\/\u2212 mice upon Con A restimulation in contrast to those from wt animals. Con A-tolerant wt mice harbored significantly increased numbers of intrahepatic CXCR3+T-bet+ Tregs that produced IL-10 compared with nontolerant animals. IFN-\u03b3 deficiency or anti\u2013IFN-\u03b3 Ab treatment demonstrated that conversion to CXCR3+T-bet+ Tregs depended on a Th1 response. Accordingly, in an immunotherapeutic approach, CD4+CD25+Foxp3+ Tregs from Con A-pretreated CXCR3-deficient mice failed to protect against Con A-induced hepatitis, whereas Tregs from Con A-tolerant wt mice allowed CXCR3-deficient mice to recover from Con A hepatitis. In summary, CXCR3+T-bet+IL-10+ Tregs are generated in the liver in dependence of IFN-\u03b3, then disseminated into the organism and specifically migrate into the liver, where they limit immune-mediated liver damage.<\/jats:p>","DOI":"10.4049\/jimmunol.1003750","type":"journal-article","created":{"date-parts":[[2011,3,26]],"date-time":"2011-03-26T04:07:28Z","timestamp":1301112448000},"page":"5284-5293","source":"Crossref","is-referenced-by-count":71,"title":["CXCR3 Deficiency Exacerbates Liver Disease and Abrogates Tolerance in a Mouse Model of Immune-Mediated Hepatitis"],"prefix":"10.1093","volume":"186","author":[{"given":"Annette","family":"Erhardt","sequence":"first","affiliation":[{"name":"Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf , D-20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Wegscheid","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf , D-20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Claass","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf , D-20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Carambia","sequence":"additional","affiliation":[{"name":"Medical Clinic I, Center of Internal Medicine, University Medical Center Hamburg-Eppendorf , D-20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Herkel","sequence":"additional","affiliation":[{"name":"Medical Clinic I, Center of Internal Medicine, University Medical Center Hamburg-Eppendorf , D-20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Willi","family":"Mittr\u00fccker","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Medical Center Hamburg-Eppendorf , D-20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Panzer","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Center of Internal Medicine, University Medical Center Hamburg-Eppendorf , D-20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisa","family":"Tiegs","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf , D-20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,5,1]]},"reference":[{"key":"2025032411233804300_r1","doi-asserted-by":"crossref","first-page":"540","DOI":"10.2741\/3261","article-title":"Chemokines and chemokine receptors: an overview","volume":"14","author":"Bonecchi","year":"2009","journal-title":"Front. 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