Molecular Immunology 2015-02-01

Adenosine A2A receptor, a potential valuable target for controlling reoxygenated DCs-triggered inflammation.

Chunmei Liu, Qianwen Shang, Yang Bai, Chun Guo, Faliang Zhu, Lining Zhang, Qun Wang

Index: Mol. Immunol. 63(2) , 559-65, (2015)

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Abstract

Dendritic cells (DCs) exposed to various oxygen tensions under physiopathological conditions are the critical immune cells linking innate and adaptive immunity. We have previously demonstrated that reoxygenation of hypoxia-differentiated DCs triggers complete DCs activation and inflammatory responses, so restraining the activation of reoxygenated DCs is important to suppress inflammatory responses in diseases caused by oxygen redelivery such as ischemia-reperfusion injury. In the current study, we showed that reoxygenation of hypoxia-differentiated DCs led to predominant expression of high levels of adenosine receptor A2AR on reoxygenated DCs as compared to those on hypoxic or normoxic DCs. Agonist CGS21680 targeting A2AR could effectively inhibit the maturation and activation of reoxygenated DCs through downregulating the expression of MHC class II molecules and CD86. In response to CGS21680 treatment, reoxygenated DCs exhibited a decrease in proinflammatory cytokines IL-1β, IL-6 and TNF-α, and an increase in immune-regulatory cytokine TGF-β. These data suggest the critical role of A2AR signaling pathway in inhibiting the maturation and proinflammatory function of reoxygenated DCs, thereby proposing A2AR as a potential valuable target for controlling reoxygenated DCs-triggered inflammation.