التفاصيل البيبلوغرافية
| العنوان: |
CCR1 Inhibition Ameliorates the Progression of Lupus Nephritis in NZB/W Mice. |
| المؤلفون: |
Bignon, Alexandre1,2, Gaudin, Françoise1,2, Hémon, Patrice1,2, Tharingei, Hugo3, Mayol, Katia4, Walzer, Thierry4, Loetscher, Pius5, Peuchmaur, Michel6,7, Berrebi, Dominique1,2,6,7, Balabanian, Karl1,2 karl.balabanian@u-psud.fr |
| المصدر: |
Journal of Immunology. 2/1/2014, Vol. 192 Issue 3, p886-896. 11p. |
| مصطلحات موضوعية: |
*CHEMOKINE receptors, *LUPUS nephritis, *AUTOIMMUNE diseases, *MACROPHAGES, *T cells, *NEUTROPHILS, *LABORATORY mice |
| مستخلص: |
Systemic lupus erythematosus is a chronic inflammatory autoimmune disease, the development of which is characterized by a progressive loss of renal function. Such dysfunction is associated with leukocyte infiltration in the glomerular and tubulointerstitial compartments in both human and experimental lupus nephritis. In this study, we investigated the role of the Cerf chemokine receptor in this infiltration process during the progression of nephritis in the lupus-prone New Zealand Black/New Zealand White (NZB/W) mouse model. We found that peripheral T cells, mononuclear phagocytes, and neutrophils, but not B cells, from nephritic NZB/W mice were more responsive to Ccrl ligands than the leukocytes from younger prenephritic NZB/W mice. Short-term treatment of nephritic NZB/W mice with the orally available Ccrl antagonist BL5923 decreased renal infiltration by T cells and macrophages. Longer Ccrl blockade decreased kidney accumulation of effector/memory CD4+ T cells, Ly6C+ monocytes, and both Ml and M2 macrophages; reduced tubulointerstitial and glomerular injuries; delayed fatal proteinuria; and prolonged animal lifespan. In contrast, renal humoral immunity was unaffected in BL5923-treated mice, which reflected the unchanged numbers of infiltrated B cells in the kidneys. Altogether, these findings define a pivotal role for Ccrl in the recruitment of T and mononuclear phagocyte cells to inflamed kidneys of NZB/W mice, which in turn contribute to the progression of renal injury. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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