Koga Tomohiro, Kawakami Atsushi
a Unit of Advanced Preventive Medical Sciences , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan.
b Center for Bioinformatics and Molecular Medicine , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan.
Mod Rheumatol. 2018 Mar;28(2):211-214. doi: 10.1080/14397595.2017.1413964. Epub 2017 Dec 20.
Calcium/calmodulin-dependent protein kinase IV (CaMK4) is a multifunctional serine/threonine kinase that regulates gene expression by activating transcription factors in a wide range of immune cells including T cells and antigen-presenting cells. The function of CaMK4 is suggested to be abnormal mainly in systemic lupus erythematosus (SLE), which is characterized by autoantibody production, immune complex formation, and immune dysregulation. Although accumulating evidence indicates that CaMK4 plays important roles in the immune responses, the precise molecular mechanisms underlying the development of autoimmune diseases and inflammatory disorders have not been established. In this review, we briefly summarize the role of CaMK4 in immune responses. We also discuss T-cell signaling pathways that control interleukin (IL)-17 production in patients with lupus nephritis and in glomerulonephritis in lupus-prone mice. A better understanding of the signaling and gene regulation of CaMK4 will lead to the identification of novel therapeutic targets in Th17 driven-autoimmune diseases.
钙/钙调蛋白依赖性蛋白激酶IV（CaMK4）是一种多功能丝氨酸/苏氨酸激酶，它通过激活包括T细胞和抗原呈递细胞在内的多种免疫细胞中的转录因子来调节基因表达。CaMK4的功能异常主要见于系统性红斑狼疮（SLE），其特征为自身抗体产生、免疫复合物形成和免疫失调。尽管越来越多的证据表明CaMK4在免疫反应中起重要作用，但自身免疫性疾病和炎症性疾病发生发展的确切分子机制尚未明确。在本综述中，我们简要总结了CaMK4在免疫反应中的作用。我们还讨论了在狼疮性肾炎患者和狼疮易感小鼠的肾小球肾炎中控制白细胞介素（IL）-17产生的T细胞信号通路。更好地理解CaMK4的信号传导和基因调控将有助于确定Th17驱动的自身免疫性疾病中的新治疗靶点。
