Immunological characteristics and clinical significance of urinary CD11c+ macrophages in lupus nephritis

Abstract

Abstract Kidney-infiltrating immune cells may be involved in the pathogenesis of lupus nephritis (LN). We aimed to analyse the immunological characteristics and clinicopathologic relevance of urinary CD11c+ macrophages in patients with LN. Compared with patients with no LN or non-proliferative LN, those with proliferative LN had significantly higher urinary levels of CD11c+ macrophages, which were strongly correlated with their anti-dsDNA antibody titer. Urinary CD11c+ macrophages expressed pro-inflammatory cytokines, such as interleukin (IL)-6 and IL-1β, and resembled infiltrated monocytes rather than tissue-resident macrophages in terms of surface marker expression. They showed high expression of the chemokine receptor CXCR3, whose cognate chemokine IP-10 was expressed by urinary tubular epithelial cells (TECs). When treated with sera from systemic lupus erythematosus patients, peripheral monocytes acquired the morphological and functional properties of urinary CD11c+ macrophages, which was blocked by DNase treatment. Finally, SLE sera treated monocytes induced fibronectin expression, apoptosis, and cell detachment in HK-2 cells via IL-6 production. Importantly, the number of urinary CD11c+ macrophages was significantly associated with chronicity indices, including tubular atrophy and interstitial fibrosis, and renal response in LN patients. CD11c+ macrophages may be involved in the pathogenesis of tubulointerstitial damage in LN.