Dendritic cells genetically engineered to express IL-4 inhibit murine collagen-induced arthritis
Dendritic cells genetically engineered to express IL-4 inhibit murine collagen-induced arthritis
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DOI：
10.1172/jci11490
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发表时间：
2001-05-01
影响因子：
15.9
通讯作者：
Fox, DA
中科院分区：
文献类型：
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作者：
Morita, Y;Yang, JM;Fox, DA
树突状细胞（dc）是一种特殊的抗原呈递细胞，从外周迁移到淋巴组织，在那里它们激活和调节T细胞。对树突状细胞进行基因修饰以表达免疫调节分子将为自身免疫性疾病和其他疾病提供新的免疫治疗策略。我们设计了表达IL-4的骨髓来源dc，并测试了这些细胞控制小鼠胶原诱导关节炎（CIA）的能力，这是一种类风湿关节炎模型，Th1细胞在其中起关键作用。il -4转导的dc在体外抑制Th1对II型胶原的反应。单次注射il -4转导的dc降低了CIA的发生率和严重程度，并抑制了既定的Th1反应和相关的体液反应，尽管注射的dc在脾脏中仅短暂持续存在。相比之下，对照dc和il -4转导的T细胞或成纤维细胞未能改变疾病的进程。功能效应与DC从注射部位向淋巴器官（尤其是脾脏）迁移的不同效率密切相关。在给予IL-4转导的dc后，脾T细胞产生IL-4以响应抗cd3的能力增强。这些结果支持了使用转基因dc治疗自身免疫性疾病的可行性。
Dendritic cells (DCs) are specialized antigen-presenting cells that migrate from the periphery to lymphoid tissues, where they activate and regulate T cells. Genetic modification of DCs to express immunoregulatory molecules would provide a new immunotherapeutic strategy for autoimmune and other diseases. We have engineered bone marrow-derived DCs that express IL-4 and tested the ability of these cells to control murine collagen-induced arthritis (CIA), a model for rheumatoid arthritis in which Th1 cells play a critical role. IL-4-transduced DCs inhibited Th1 responses to collagen type II in vitro. A single injection of IL-4-transduced DCs reduced the incidence and severity of CIA and suppressed established Th1 responses and associated humoral responses, despite only transient persistence of injected DCs in the spleen. In contrast, control DCs and IL-4-transduced T cells or fibroblastic cells failed to alter the course of the disease. The functional effects correlated well with the differential efficiency of DC migration from various sites of injection to lymphoid organs, especially the spleen. The ability of splenic T cells to produce IL-4 in response to anti-CD3 was enhanced after the administration of IL-4-transduced DCs. These results support the feasibility of using genetically modified DCs for the treatment of autoimmune disease.