Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Rheumatology (Oxford). 2020 Aug 1;59(8):2135-2145. doi: 10.1093/rheumatology/keaa053.
Kidney-infiltrating immune cells can contribute to the pathogenesis of lupus nephritis (LN). We investigated the immunological characteristics of CD11c+ macrophages and their functions associated with the pathogenesis of LN.
CD11c+ macrophages were examined in the urine samples of patients with LN. Phenotypic markers and pro-inflammatory cytokine expression levels were analysed by flow cytometry. To determine the origin of urinary macrophages, peripheral monocytes were treated with sera from patients with systemic lupus erythematosus (SLE). The pathogenic role of CD11c+ macrophages in tubulointerstitial damage was investigated using SLE sera-treated monocytes and HK-2 cells.
Urinary CD11c+ macrophages expressed pro-inflammatory cytokines, such as IL-6 and IL-1β, and resembled infiltrated monocytes rather than tissue-resident macrophages with respect to surface marker expression. CD11c+ macrophages had high expression levels of the chemokine receptor CXCR3, which were correlated with cognate chemokine IP-10 expression in urinary tubular epithelial cells. When treated with sera from SLE patients, peripheral monocytes acquired the morphological and functional characteristics 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 production of IL-6.
CD11c+ macrophages may be involved in the pathogenesis of tubulointerstitial injury in LN.
浸润肾脏的免疫细胞可能有助于狼疮肾炎 (LN) 的发病机制。我们研究了 CD11c+巨噬细胞的免疫学特征及其与 LN 发病机制相关的功能。
检测 LN 患者尿液样本中的 CD11c+巨噬细胞。通过流式细胞术分析其表型标志物和促炎细胞因子表达水平。为了确定尿巨噬细胞的起源，用系统性红斑狼疮 (SLE) 患者的血清处理外周单核细胞。用 SLE 血清处理的单核细胞和 HK-2 细胞来研究 CD11c+巨噬细胞在肾小管间质损伤中的致病作用。
尿 CD11c+巨噬细胞表达促炎细胞因子，如 IL-6 和 IL-1β，其表面标志物表达类似于浸润的单核细胞，而不是组织驻留的巨噬细胞。CD11c+巨噬细胞高表达趋化因子受体 CXCR3，与尿肾小管上皮细胞中同源趋化因子 IP-10 的表达相关。用 SLE 患者的血清处理后，外周单核细胞获得了尿 CD11c+巨噬细胞的形态和功能特征，该特征可被 DNAse 处理所阻断。最后，SLE 血清处理的单核细胞通过产生 IL-6 诱导 HK-2 细胞中纤维连接蛋白表达、细胞凋亡和细胞脱落。
CD11c+巨噬细胞可能参与 LN 肾小管间质损伤的发病机制。
