猪RIG-I样受体（RLR）RIG-I、MDA5和LGP2相互关系及其表达调控研究

天然免疫是免疫系统的第一道防线，通过模式分子受体（PRR）识别病原、激活细胞信号、产生抗病原效应分子、影响下游特异性免疫应答。 RIG-I样受体（RLR)是细胞胞浆内主要的PRR受体家族，在识别病毒RNA和抗病毒方面起关键作用。猪RLR与猪多种传染性疫病病原尤其是致病病毒存在复杂的相互作用，并在激发保护性免疫方面起关键作用，但目前缺少免疫生物学研究。 本申请针对猪RLR家族所有的三个成员RIG-I、MDA5和LGP2进行系统性研究，包括三者的信号功能、RIG-I和MDA5的功能重叠性、LGP2对RIG-I和MDA5的调控及作用机制；RIG-I和MDA5识别配体RNA的差异，激发下游表达基因的差异；三者在组织和细胞中的分布和表达，三者基因诱导表达调控的细节等。我们前期实验结果表明，猪RLR和人RLR表现出特征性的种属差异，提示这一研究方向值得我们进一步地探索和追寻。

The innate immunity is the first line of defense, via the pattern-recognition receptors (PRR), it recognizes pathogens, triggers intra-cellular signaling, produces anti-pathogen molecules, shapes downstream adaptive immune responses. RIG-I like receptors (RLR) are the major cytosol PRR family for virus recognition, play a critical role in the recognition of viral RNA and anti-viral immunity. Porcine RLR have intricate interactions with various pig infectious disease pathogens especially pathogenic viruses, and are the key for eliciting protective immune responses. However, there is a lack of immunobiological research on porcine RLR. This application proposes the systemic research on all three porcine RLR members, RIG-I,MDA5 and LGP2, which encompasses the signaling functions of three receptors, the redundancy between RIG-I and MDA5, the regulations of RIG-I and MDA5 by LGP2 and the underlying mechanism; the differences of the binding agonist RNAs, and the downstream activated genes between RIG-I and MDA5; the distributions and expressions of three porcine receptors in various tissues and cell types, and the details for gene induction regulations of three receptors. Our preliminary data show that porcine RLR exhibit characteristic difference from human RLR, which motivates us to further explore and pursue along this direction.