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We assessed chemotactic responsiveness of CD4+ T-cells to CXCL12, the effect of AMD3100, a CXC chemokine receptor 4 (CXCR4) antagonist, in mice and lymphocytes from patients with NAFLD, and the affinity of CXCL12 for CXCR4. CXCL12-promoted migration of CD4+ T-cells from three different mouse models of NASH was increased and dependent of CXCR4. CD4+ T-cells from patients with NASH, but not from patients with pure steatosis, responded more strongly to the chemotactic effect of CXCL12, and this response was inhibited by AMD3100. Treatment with AMD3100 decreased the number of CD4+ T-cells to the liver in ob\/ob mice. CXCL12 expression in the liver, CXCR4 and CXCR7 expression in CD4+ T-cells were not increased in three different mouse models of NASH. However, the affinity of CXCL12 for CXCR4 was increased in CD4+ T-cells of ob\/ob mice. In conclusion, the CXCL12\/CXCR4 pathway contributes in both mice and patients to the enhanced recruitment of CD4+ T-cells in NASH. An increased affinity of CXCL12 to CXCR4 rather than a higher expression of the chemokine or its receptors is involved in this process.<\/jats:p>","DOI":"10.1042\/cs20130833","type":"journal-article","created":{"date-parts":[[2014,7,31]],"date-time":"2014-07-31T06:28:14Z","timestamp":1406788094000},"page":"257-267","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["CXCR4 dysfunction in non-alcoholic steatohepatitis in mice and patients"],"prefix":"10.1042","volume":"128","author":[{"given":"H\u00e9dia","family":"Boujedidi","sequence":"first","affiliation":[{"name":"Univ Paris-Sud, Facult\u00e9 de M\u00e9decine Paris-Sud, Kremlin-Bic\u00eatre, France"},{"name":"INSERM U996, Clamart, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Robert","sequence":"additional","affiliation":[{"name":"Univ Paris-Sud, Facult\u00e9 de M\u00e9decine Paris-Sud, Kremlin-Bic\u00eatre, 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