Previous studies have shown that CD73 is pivotal in the conversion of pro-inflammatory adenosine triphosphate into anti-inflammatory adenosine and that immune cells of the same type that express different levels of CD73 are functionally distinct. In this study we show that adenosine enhances the Th17 promoting effect of dendritic cells (DCs), and DCs expressing CD73 critically augment Th17 responses. Bone marrow dendritic cells (BMDCs) do not constantly express CD73; however, a significant portion of the BMDCs expressed CD73 after exposure to Toll-like receptor ligand, leading to stronger Th17 responses by converting adenosine monophosphate to adenosine. We show that the CD73⁺ BMDCs play a critical role in cascading Th17 responses, and CD73⁺ BMDCs are functionally augmented after treatment with Toll-like receptor ligand. Splenic antigen presenting cells (DCs) of CD73^−/− mouse have a poor Th17-stimulating effect, even after exposure to lipopolysaccharide (LPS) or γδ T cells, indicating that induction of CD73⁺ DCs is critically involved in augmented Th17 responses. We conclude that CD73⁺ DCs critically trigger cascading Th17 responses, and the activated Th17 cells that express CD73 further augment Th17 responses, leading to cascading exacerbation. Hence, disabling the CD73 function of DCs should block this cascading response and mitigate Th17 responses.

先前的研究表明，CD73 在促炎三磷酸腺苷转化为抗炎腺苷的过程中至关重要，并且表达不同水平 CD73 的同一类型免疫细胞在功能上是不同的。在这项研究中，我们表明腺苷可增强树突细胞 (DC) 的 Th17 促进作用，并且表达 CD73 的 DC 可显着增强 Th17 反应。骨髓树突细胞 (BMDCs) 不持续表达 CD73；然而，在暴露于 Toll 样受体配体后，很大一部分 BMDC 表达 CD73，通过将单磷酸腺苷转化为腺苷导致更强的 Th17 反应。我们表明 CD73 ⁺ BMDCs 在级联 Th17 反应中起关键作用，而 CD73 ⁺BMDCs 在用 Toll 样受体配体治疗后功能增强。CD73 ^-/-小鼠的脾抗原呈递细胞 (DC)具有较差的 Th17 刺激作用，即使在暴露于脂多糖 (LPS) 或 γδ T 细胞后，表明 CD73 ⁺ DC 的诱导与增强的 Th17 反应密切相关。我们得出结论，CD73 ⁺ DCs 严重触发级联 Th17 反应，表达 CD73 的活化 Th17 细胞进一步增强 Th17 反应，导致级联恶化。因此，禁用 DC 的 CD73 功能应该会阻止这种级联反应并减轻 Th17 反应。