Optineurin inhibition impedes type II collagen challenged dendritic cell migration

Due to the maturation, migration and antigen presentation functions, dendritic cells (DCs) play a central role in the development of many autoimmune diseases, like rheumatoid arthritis, multiple sclerosis and dermatitis. However, the molecular regulatory process of disease- or antigen-specific DC activation remains elusive. We show that deletion of Optineurin (OPTN) effectively impairs type II collagen (CII), the main autoantigen for rheumatoid arthritis, challenged DC migration, thus ameliorating collagen-induced arthritis. Transcriptome analyses indicate that OPTN promotes the expressions of migration related genes. Our findings thus indicate that OPTN is an important regulator of CII-pulsed DC migration, which may be of potential value for the accurate treatment of rheumatoid arthritis. 3 wild type and 3 OPTN knockout CII-stimulated BMDCs

鉴于树突状细胞（dendritic cells, DCs）具备成熟、迁移及抗原呈递功能，其在类风湿关节炎、多发性硬化与皮炎等多种自身免疫疾病的发生发展中发挥核心作用。然而，疾病特异性或抗原特异性的DC活化的分子调控过程仍不明晰。本研究证实，敲除视神经蛋白（Optineurin, OPTN）可有效抑制类风湿关节炎主要自身抗原II型胶原（type II collagen, CII）刺激诱导的DC迁移，进而改善胶原诱导性关节炎。转录组分析结果显示，OPTN可促进迁移相关基因的表达。综上，OPTN是CII脉冲处理的DC迁移的重要调控因子，其或可为类风湿关节炎的精准治疗提供潜在应用价值。本研究使用了3株野生型与3株OPTN敲除的经CII刺激的骨髓来源树突状细胞（bone marrow-derived dendritic cells, BMDCs）。