烟酸在临床上被用来治疗高血脂和心血管系统疾病已有50多年历史。2003年，HCA2被发现是烟酸的作用靶点，随后不久，它的内源性配体3-羟基丁酸被发现。烟酸可以通过HCA2，激活Gi蛋白，通过信号转导，最后抑制酯酶的活性，从而起到抗脂解的功能。目前已经有多系列以HCA2为靶标的化合物已经被合成，试图开发治疗高血脂和心血管疾病的新药物。除了在脂肪细胞中表达以外，HCA2还在多种免疫细胞中表达，包括中心粒细胞，巨噬细胞，树状细胞以及上皮朗格罕氏细胞。HCA2在免疫细胞中的广泛存在意味着它在免疫系统有重要功能，但其功能目前知之甚少。本项目将在原有研究基础上，选择内源性表达HCA2的免疫细胞，并结合HCA2 knock-out小鼠动物模型，对HCA2在免疫细胞中的信号转导及功能做深入研究，试图揭示HCA2在免疫细胞中的作用机理，为新靶标新药物的发现，烟酸进一步的临床应用奠定基础。

Nicotinic acid has been used clinically to treat hyperlipidemia and coronary heart disease for over 50 years. In 2003, the human and mouse orphan G-protein-coupled receptor HCA2 was discovered to be receptor for nicotinic acid. Shortly there after, the ketone body 3-hydroxy-butyrate was shown to be an endogenous ligand for HCA2. Nicotinic acid was shown to act through HCA2 and induce signal transduction through Gi protein to inhibit homon-sensitive lipase and result in antilipolytic effects in fat cells. Up to now, many ligands of HCA2 have been synthesized to develop new drugs to treat hyperlipidemia and coronary heart disease. Apart from adipocytes, expression of HCA2 is also found in various immune cells, including neutrophils, macrophages, dendritic cells, and epidermal Langerhans cells. The broad expression of HCA2 in immune cells means its possible important roles in immune systems, but the roles is known little. Based on our previous study, this project will use immune cells expressing HCA2 and HCA2 knock-out mouse models to study the HCA2-mediated signal transduction and function in immune cells. This study is tried to reveal the functional mechanism of HCA2 in immune cells and the work maybe help to further exploring new therapeutic targets, new drugs and new clinical using of nicotinic acid.