Kim Adam, McCullough Rebecca L, Poulsen Kyle L, Sanz-Garcia Carlos, Sheehan Megan, Stavitsky Abram B, Nagy Laura E
Department of Pathobiology, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA.
Department of Molecular Medicine, Case Western Reserve University, Cleveland, OH, USA.
Handb Exp Pharmacol. 2018;248:347-367. doi: 10.1007/164_2017_88.
Both the innate and adaptive immune systems are critical for the maintenance of healthy liver function. Immune activity maintains the tolerogenic capacity of the liver, modulates hepatocellular response to various stresses, and orchestrates appropriate cellular repair and turnover. However, in response to heavy, chronic alcohol exposure, the finely tuned balance of pro- and anti-inflammatory functions in the liver is disrupted, leading to a state of chronic inflammation in the liver. Over time, this non-resolving inflammatory response contributes to the progression of alcoholic liver disease (ALD). Here we review the contributions of the cellular components of the immune system to the progression of ALD, as well as the pathophysiological roles for soluble and circulating mediators of immunity, including cytokines, chemokines, complement, and extracellular vesicles, in ALD. Finally, we compare the role of the innate immune response in health and disease in the liver to our growing understanding of the role of neuroimmunity in the development and maintenance of a healthy central nervous system, as well as the progression of neuroinflammation.
先天性免疫系统和适应性免疫系统对于维持肝脏的健康功能都至关重要。免疫活动维持肝脏的免疫耐受能力，调节肝细胞对各种应激的反应，并协调适当的细胞修复和更新。然而，在长期大量饮酒的情况下，肝脏中促炎和抗炎功能的精细平衡被打破，导致肝脏处于慢性炎症状态。随着时间的推移，这种无法消退的炎症反应会促使酒精性肝病（ALD）的进展。在这里，我们综述免疫系统的细胞成分对ALD进展的作用，以及免疫的可溶性和循环介质（包括细胞因子、趋化因子、补体和细胞外囊泡）在ALD中的病理生理作用。最后，我们将肝脏中先天性免疫反应在健康和疾病中的作用，与我们对神经免疫在健康中枢神经系统的发育和维持以及神经炎症进展中的作用的日益深入的理解进行比较。
