The differential characterization of GPR55 receptor in human peripheral blood reveals a distinctive expression in monocytes and NK cells and a proinflammatory role in these innate cells
The differential characterization of GPR55 receptor in human peripheral blood reveals a distinctive expression in monocytes and NK cells and a proinflammatory role in these innate cells
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DOI：
10.1093/intimm/dxu097
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发表时间：
2015-03-01
影响因子：
4.4
通讯作者：
Maccarrone, Mauro
中科院分区：
文献类型：
--
作者：
Chiurchiu, Valerio;Lanuti, Mirko;Maccarrone, Mauro
G蛋白偶联受体55（GPR 55）由内源性，植物来源和合成大麻素激活。最近的研究报告了GPR 55的广泛组织分布，并发现该受体在炎症性疼痛，肠道和骨骼生理学以及癌症中的重要作用。然而，对GPR 55在免疫细胞中的表达和功能知之甚少。为了解决这个问题，我们使用多色流式细胞术对不同的人类先天性和适应性免疫群体中的GPR 55进行了详细的表征，并且我们发现与适应性免疫的几种细胞相比，单核细胞和NK细胞表达了显着水平的这种受体。在LPS激活的单核细胞中，特异性激动剂O-1602激活GPR 55可促进IL-12和TNF-α的产生，并降低内吞活性。此外，它增加了由IL-2和IL-12激活的NK细胞中的CD 69活化标志物表达、颗粒酶B和CD 107 a依赖性细胞毒性以及IFN-γ和TNF-α的产生。GPR 55的这些过度刺激作用被其选择性拮抗剂大麻二酚拮抗。总之，我们的数据揭示了GPR 55在先天免疫中的促炎作用，这可能对设计新的免疫治疗策略很重要。
G protein-coupled receptor 55 (GPR55) is activated by endogenous, plant-derived and synthetic cannabinoids. Recent studies reported a broad tissue distribution for GPR55 and found prominent roles for this receptor in inflammatory pain, gut and bone physiology, as well as cancer. However, little is known about the expression and function of GPR55 in immune cells. To address this question, we performed a detailed characterization of GPR55 in different human innate and adaptive immune populations using polychromatic flow cytometry and we found that monocytes and NK cells expressed remarkable levels of this receptor compared to several cells of adaptive immunity. GPR55 activation by the specific agonist O-1602 boosted IL-12 and TNF-alpha production, and decreased endocytic activity, in LPS-activated monocytes. In addition, it increased CD69 activation marker expression, granzyme B and CD107a-dependent cytotoxicity and IFN-gamma and TNF-alpha production in NK cells activated by both IL-2 and IL-12. These over-stimulatory effects of GPR55 were antagonized by its selective antagonist cannabidiol. Altogether, our data thus unveil a proinflammatory role for GPR55 in innate immunity that may be important for the design of new immune therapeutic strategies.