The role of renal infiltrating CD11c+ cells in lupus nephritis

Lupus nephritis, a leading cause of morbidity and mortality in patients with Systemic Lupus Erythematosus (SLE), manifests as inflammatory infiltration of the kidney. Many types of leukocytes infiltrate the kidney during the progression of lupus nephritis, but the specific contributions of each infiltrating population are still unclear. In this study, we have found that CD11c+cells accumulate in nephritic kidneys of lupus-prone mice. These renal CD11c+ cells, forming clusters with infiltrating T cells, are proinflammatory and secreting cytokines that promote autoantibody production and Th17 response. They also produce chemokines that attract other leukocytes into the kidney. The surface phenotype (CD11b+CD115highCD135lowCX3CR1highFcgRIVhigh)suggests that they may be derived from mature monocytes and be activated by pathogenic immune complexes. Ex vivo co-culture experiments also suggest that they can maintain the survival of renal infiltrating T cells. To further demonstrate the role of these CD11c+ cells in vivo, we are currently depleting them by targeting CX3CR1, as they are a unique population of cells predominantly expressing a high level of CX3CR1. The results obtained from this study will be important for the understanding of lupus pathogenesis and identification of new therapeutic targets against lupus nephritis.