2019年11月27日出版的《细胞》杂志报道了德国慕尼黑大学Veit Hornung、Thomas Carell等研究人员合作完成的工作，他们的研究表明TLR8是RNA酶T2降解产物的感知分子。

研究人员发现溶酶体内核糖核酸酶RNA酶T2是TLR8依赖性RNA识别的非冗余上游成分。要使TLR8可检测到复杂的单链外源RNA分子，需要RNA酶T2活性。这是由于RNA酶T2在嘌呤和尿苷残基之间优先裂解单链RNA分子，这对分解代谢性尿苷的供应和嘌呤2'，3'-环磷酸酯封端的寡核糖核苷酸的产生至关重要。如此产生的分子构成TLR8的第一和第二结合口袋的激动性配体。

总之，这些结果确定了由TLR8感知的RNA来源分子模式的身份和起源。

据悉，TLR8是人类髓样区室中表达最高的模式识别受体之一，但对其作用方式知之甚少。TLR8接合两个不同的配体结合位点以检测RNA降解产物，尽管目前尚不清楚在复杂RNA分子检测中这些配体如何形成。

附：英文原文

Title: TLR8 Is a Sensor of RNase T2 Degradation Products

Author: Wilhelm Greulich, Mirko Wagner, Moritz M. Gaidt, Che Stafford, Yiming Cheng, Andreas Linder, Thomas Carell, Veit Hornung

Issue&Volume: 2019/11/27

Abstract: TLR8 is among the highest-expressed pattern-recognition receptors in the human myeloidcompartment, yet its mode of action is poorly understood. TLR8 engages two distinctligand binding sites to sense RNA degradation products, although it remains unclearhow these ligands are formed in cellulo in the context of complex RNA molecule sensing. Here, we identified the lysosomalendoribonuclease RNase T2 as a non-redundant upstream component of TLR8-dependentRNA recognition. RNase T2 activity is required for rendering complex single-stranded,exogenous RNA molecules detectable for TLR8. This is due to RNase T2’s preferentialcleavage of single-stranded RNA molecules between purine and uridine residues, whichcritically contributes to the supply of catabolic uridine and the generation of purine-2′,3′-cyclophosphate-terminatedoligoribonucleotides. Thus-generated molecules constitute agonistic ligands for thefirst and second binding pocket of TLR8. Together, these results establish the identityand origin of the RNA-derived molecular pattern sensed by TLR8.

DOI: 10.1016/j.cell.2019.11.001

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31222-X