CXCR4 dysfunction in non-alcoholic steatohepatitis in mice and patients
| Autor: | Sylvie Naveau, Patrice Hemon, Karl Balabanian, Dominique Emilie, Olivier Robert, Hélène Gary-Gouy, Sophie Prevot, Marie-Laure Renoud, Gabriel Perlemuter, Hédia Boujedidi, Françoise Bachelerie, Hugo Tharinger, Alexandre Bignon, Anne-Marie Cassard-Doulcier |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Benzylamines Receptors CXCR4 medicine.medical_specialty Chemokine Mice Obese Biology Cyclams CXCR4 Cell Movement Heterocyclic Compounds Non-alcoholic Fatty Liver Disease Internal medicine medicine Animals Humans Lymphocyte Count CXC chemokine receptors Receptor Receptors CXCR Fatty liver Chemotaxis General Medicine Middle Aged medicine.disease Chemokine CXCL12 digestive system diseases biological factors Up-Regulation Mice Inbred C57BL Disease Models Animal Endocrinology embryonic structures biology.protein Female biological phenomena cell phenomena and immunity Steatosis Steatohepatitis |
| Zdroj: | Clinical Science. 128:257-267 |
| ISSN: | 1470-8736 0143-5221 |
| DOI: | 10.1042/cs20130833 |
| Popis: | Homing of inflammatory cells to the liver is key in the progression of non-alcoholic steatohepatitis (NASH). An abnormal response of CD4+ T-cells from obese mice to the chemotactic effect of CXCL12 has been reported but the mechanism involved in this process and relevance in patients are unknown. We aimed to explore the mechanism involved in the abnormal chemotaxis of CXC chemokine ligand 12 (CXCL12) in several mouse models of NASH and the relevance in the context of human non-alcoholic fatty liver disease (NAFLD). 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. |
| Databáze: | OpenAIRE |
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