Murphy Michael B, Medvedev Andrei E
Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, USA.
Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, USA
J Leukoc Biol. 2016 Jun;99(6):839-50. doi: 10.1189/jlb.2RU1215-575R. Epub 2016 Mar 10.
Sensing of microbial pathogens and endogenous "alarmins" by macrophages and dendritic cells is reliant on pattern recognition receptors, including membrane-associated TLRs, cytosolic nucleotide-binding and oligomerization domain leucine-rich repeat-containing receptors, retinoic acid-inducible gene I-like receptors, and absent in melanoma 2-like receptors. Engagement of TLRs elicits signaling pathways that activate inflammatory genes whose expression is regulated by chromatin-modifying complexes and transcription factors. Long noncoding RNAs have emerged as new regulators of inflammatory mediators in the immune system. They are expressed in macrophages, dendritic cells, neutrophils, NK cells, and T- and B-lymphocytes and are involved in immune cell differentiation and activation. Long noncoding RNAs act via repression or activation of transcription factors, modulation of stability of mRNA and microRNA, regulation of ribosome entry and translation of mRNAs, and controlling components of the epigenetic machinery. In this review, we focus on recent advances in deciphering the mechanisms by which long noncoding RNAs regulate TLR-driven responses in macrophages and dendritic cells and discuss the involvement of long noncoding RNAs in endotoxin tolerance, autoimmune, and inflammatory diseases. The dissection of the role of long noncoding RNAs will improve our understanding of the mechanisms of regulation of inflammation and may provide new targets for therapeutic intervention.
巨噬细胞和树突状细胞对微生物病原体和内源性“警报素”的感知依赖于模式识别受体，包括膜相关的Toll样受体（TLR）、胞质核苷酸结合和寡聚化结构域富含亮氨酸重复序列的受体、视黄酸诱导基因I样受体以及黑色素瘤缺失2样受体。TLR的激活引发信号通路，激活由染色质修饰复合物和转录因子调控表达的炎症基因。长链非编码RNA已成为免疫系统中炎症介质的新调节因子。它们在巨噬细胞、树突状细胞、中性粒细胞、自然杀伤细胞以及T和B淋巴细胞中表达，并参与免疫细胞的分化和激活。长链非编码RNA通过抑制或激活转录因子、调节mRNA和微小RNA的稳定性、调控核糖体进入和mRNA翻译以及控制表观遗传机制的组成部分来发挥作用。在本综述中，我们重点关注在解读长链非编码RNA调节巨噬细胞和树突状细胞中TLR驱动反应的机制方面的最新进展，并讨论长链非编码RNA在内毒素耐受、自身免疫和炎症性疾病中的作用。剖析长链非编码RNA的作用将增进我们对炎症调节机制的理解，并可能为治疗干预提供新的靶点。
