Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Clin Immunol. 2024 May;262:110177. doi: 10.1016/j.clim.2024.110177. Epub 2024 Mar 8.
Calcium/calmodulin-dependent protein kinase IV (CaMK4) serves as a pivotal mediator in the regulation of gene expression, influencing the activity of transcription factors within a variety of immune cells, including T cells. Altered CaMK4 signaling is implicated in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and psoriasis, which are characterized by dysregulated immune responses and clinical complexity. These conditions share common disturbances in immune cell functionality, cytokine production, and autoantibody generation, all of which are associated with disrupted calcium-calmodulin signaling. This review underscores the consequences of dysregulated CaMK4 signaling across these diseases, with an emphasis on its impact on Th17 differentiation and T cell metabolism-processes central to maintaining immune homeostasis. A comprehensive understanding of roles of CaMK4 in gene regulation across various autoimmune disorders holds promise for the development of targeted therapies, particularly for diseases driven by Th17 cell dysregulation.
钙/钙调蛋白依赖性蛋白激酶 IV（CaMK4）作为基因表达调控的关键介质，影响多种免疫细胞（包括 T 细胞）中转录因子的活性。CaMK4 信号转导的改变与自身免疫性疾病有关，如系统性红斑狼疮、类风湿关节炎和银屑病，这些疾病的特点是免疫反应失调和临床复杂性。这些疾病的共同特点是免疫细胞功能、细胞因子产生和自身抗体生成紊乱，所有这些都与钙-钙调蛋白信号转导的破坏有关。本综述强调了 CaMK4 信号转导失调在这些疾病中的后果，重点关注其对 Th17 分化和 T 细胞代谢的影响，这些过程对维持免疫稳态至关重要。全面了解 CaMK4 在各种自身免疫性疾病中的基因调控作用，有望为靶向治疗的发展提供帮助，特别是针对由 Th17 细胞失调驱动的疾病。
