Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova 595, Vestec 252 50, Czech Republic.
Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, Olomouc 779 00, Czech Republic.
Cytokine Growth Factor Rev. 2022 Aug;66:1-14. doi: 10.1016/j.cytogfr.2022.04.001. Epub 2022 Apr 20.
IL-6 is considered one of the well characterized cytokines exhibiting homeostatic, pro- and anti-inflammatory activities, depending on the receptor variant and the induced intracellular cis- or trans-signaling responses. IL-6-activated pathways are involved in the regulation of cell proliferation, survival, differentiation, and cell metabolism changes. Deviations in IL-6 levels or abnormal response to IL-6 signaling are associated with several autoimmune diseases including IgA nephropathy (IgAN), one of most frequent primary glomerulonephritis worldwide. IgAN is associated with increased plasma concentration of IL-6 and increased plasma concentration of aberrantly galactosylated IgA1 immunoglobulin (Gd-IgA1). Gd-IgA1 is specifically recognized by autoantibodies, leading to the formation of circulating immune complexes (CIC) with nephritogenic potential, since CIC deposited in the glomerular mesangium induce mesangial cells proliferation and glomerular injury. Infection of the upper respiratory or digestive tract enhances IL-6 production and in IgAN patients is often followed by the macroscopic hematuria. This review recapitulates general aspects of IL-6 signaling and summarizes experimental evidences about IL-6 involvement in the etiopathogenesis of IgA nephropathy through the production of Gd-IgA1 and regulation of mesangial cell proliferation.
白细胞介素 6（IL-6）被认为是一种特征明确的细胞因子，根据受体变体和诱导的细胞内顺式或反式信号转导反应，表现出稳态、促炎和抗炎活性。IL-6 激活的途径参与细胞增殖、存活、分化和细胞代谢变化的调节。IL-6 水平的偏差或对 IL-6 信号的异常反应与几种自身免疫性疾病有关，包括 IgA 肾病（IgAN），这是全球最常见的原发性肾小球肾炎之一。IgAN 与血浆中 IL-6 浓度升高和异常半乳糖化 IgA1 免疫球蛋白（Gd-IgA1）浓度升高有关。Gd-IgA1 被自身抗体特异性识别，导致具有肾毒性的循环免疫复合物（CIC）的形成，因为沉积在肾小球系膜中的 CIC 诱导系膜细胞增殖和肾小球损伤。上呼吸道或消化道感染会增强 IL-6 的产生，在 IgAN 患者中，常伴有肉眼血尿。本文综述了 IL-6 信号转导的一般方面，并总结了通过产生 Gd-IgA1 和调节系膜细胞增殖，IL-6 参与 IgA 肾病发病机制的实验证据。
