Jihye Kim1,2, Ji Hye Jeong1,2, Jaehyung Jung1,2, Hanwool Jeon3, Seungjoo Lee3, Joon Seo Lim4, Heounjeong Go5, Ji Seon Oh4, Yong-Gil Kim1, Chang-Keun Lee1, Bin Yoo1, Seokchan Hong1. 1. Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 2. Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 3. Department of Neurosurgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 4. Clinical Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 5. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: CD11c+ macrophages may be involved in the pathogenesis of tubulointerstitial injury in LN.
OBJECTIVES: 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. METHODS: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. RESULTS: 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 SLEpatients, 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. CONCLUSION:CD11c+ macrophages may be involved in the pathogenesis of tubulointerstitial injury in LN.
Authors: Ana Karina Aranda-Rivera; Anjali Srivastava; Alfredo Cruz-Gregorio; José Pedraza-Chaverri; Shrikant R Mulay; Alexandra Scholze Journal: Antioxidants (Basel) Date: 2022-01-27
Authors: Xingwang Zhao; Lan Ge; Juan Wang; Zhiqiang Song; Bing Ni; Xiaochong He; Zhihua Ruan; Yi You Journal: Front Immunol Date: 2022-02-07 Impact factor: 7.561