Baylor Institute for Immunology Research, Dallas, TX 75204;
Human Immune Monitoring Center, Institute for Immunity, Transplantation, and Infection, Stanford University Medical Center, Stanford, CA 94305;
J Immunol. 2014 Jun 15;192(12):5586-98. doi: 10.4049/jimmunol.1301319. Epub 2014 May 14.
Blood monocytes from children with systemic lupus erythematosus (SLE) behave similar to dendritic cells (DCs), and SLE serum induces healthy monocytes to differentiate into DCs in a type I IFN-dependent manner. In this study, we found that these monocytes display significant transcriptional changes, including a prominent IFN signature, compared with healthy controls. Few of those changes, however, explain DC function. Exposure to allogeneic T cells in vitro reprograms SLE monocytes to acquire DC phenotype and function, and this correlates with both IFN-inducible (IP10) and proinflammatory cytokine (IL-1β and IL6) expression. Furthermore, we found that both IFN and SLE serum induce the upregulation of CCR7 transcription in these cells. CCR7 protein expression, however, requires a second signal provided by TLR agonists such as LPS. Thus, SLE serum "primes" a subset of monocytes to readily (<24 h) respond to TLR agonists and acquire migratory DC properties. Our findings might explain how microbial infections exacerbate lupus.
系统性红斑狼疮（SLE）患儿的血液单核细胞表现类似于树突状细胞（DC），SLE 血清以 I 型干扰素（IFN）依赖的方式诱导健康单核细胞分化为 DC。在这项研究中，我们发现与健康对照组相比，这些单核细胞表现出明显的转录变化，包括显著的 IFN 特征。然而，这些变化很少能解释 DC 的功能。体外暴露于同种异体 T 细胞可重新编程 SLE 单核细胞获得 DC 表型和功能，这与 IFN 诱导（IP10）和促炎细胞因子（IL-1β和 IL6）的表达相关。此外，我们发现 IFN 和 SLE 血清均可诱导这些细胞中 CCR7 转录的上调。然而，CCR7 蛋白表达需要 TLR 激动剂（如 LPS）提供的第二信号。因此，SLE 血清“启动”了单核细胞的一个亚群，使其能够迅速（<24 小时）对 TLR 激动剂作出反应并获得迁移性 DC 特性。我们的发现可能解释了为什么微生物感染会加重狼疮。
