{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T06:15:58Z","timestamp":1697436958999},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,8,20]],"date-time":"2008-08-20T00:00:00Z","timestamp":1219190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:p><jats:bold>Aim:\u2002<\/jats:bold> CD44 has a variety of functions in immune regulation and signal transduction. Although CD44 is involved in the induction of several inflammatory diseases, it remains unknown whether CD44\u2010targeting therapies are useful for liver diseases. Here, we examined whether CD44 blockade is effective in a chemical\u2010induced liver injury model.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> We injected CD44 knock out (KO) or wild type mice with carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) and examined the difference of liver injury by immunological or histological analysis.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Although CD44KO mice exhibited suppressed liver injury at 6\u2003h after CCl<jats:sub>4<\/jats:sub> injection with decreased inflammatory cell numbers and cytokine production, these mice showed severe liver injury at 24\u2003h. We found that NKT cells played an important role in liver injury with increased infiltration of theliver after migration, which was independent of the CD44 pathway. In CD44NKT double\u2010KO mice, liver injury was suppressed with reduced cytokine production and macrophage infiltration compared with CD44KO mice. Furthermore, MIP\u20102 derived from NKT cells or tumor necrosis factor alpha from macrophages contributed to exacerbation of the liver injury, since neutralization of MIP\u20102 provided significant protection against liver injury in CD44KO mice. Finally, we found that CD44KO mice exhibited excessive liver fibrosis compared with wild\u2010type mice after repeated CCl<jats:sub>4<\/jats:sub> injections.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> We found that CD44 has unique characteristics for inflammatory liver diseases associated with NKT cell infiltration and activation. Furthermore, CD44\u2010targeting therapies may need to be viewed with caution for liver diseases due to the actions of the liver immune system.<\/jats:p>","DOI":"10.1111\/j.1872-034x.2008.00409.x","type":"journal-article","created":{"date-parts":[[2008,8,21]],"date-time":"2008-08-21T03:42:06Z","timestamp":1219290126000},"page":"93-105","source":"Crossref","is-referenced-by-count":5,"title":["Pathological role of CD44 on NKT cells in carbon tetrachloride\u2010mediated liver 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