Cancer and Inflammation Program, National Cancer Institute, 1050 Boyles Street, Frederick, MD 21702, USA.
J Autoimmun. 2009 Nov-Dec;33(3-4):275-81. doi: 10.1016/j.jaut.2009.07.010. Epub 2009 Aug 13.
Natural killer (NK) and NKT cells are a first line of defense against pathogens and transformed cells. However, dysregulation of their function can lead to autoimmune disease. A better understanding of the mechanisms controlling NK and NKT effector function should lead to the development of improved strategies for the treatment of many diseases. The site in which NK and NKT cells reside should be taken into account, because accumulating evidence suggests that the tissue microenvironment strongly influences their function. In this regard, the liver represents a unique immunologic organ in which the balance between the need for tolerance and the ability to respond rapidly to pathogens and tissue injury is tightly regulated. NK cells in the liver have augmented cytolytic activity as compared to other organs, which is consistent with a role for liver-associated NK cells in being critical effector cells for inhibiting tumor metastasis in the liver. Several studies also suggest that hepatic NKT cells have different functions than those in other organs. Whereas splenic and thymic NKT cells have been shown to suppress diabetes development, facilitate the induction of systemic tolerance and are regulated by IL-4 and other Th2 cytokines, certain subsets of NKT cells in the liver are important sources of Th1 cytokines such as Interferon gamma, and are the primary mediators of anti-tumor responses. The unique properties and roles as critical effector cells make NK and NKT cells within the liver microenvironment attractive targets of immunotherapeutic approaches that have the goal of controlling tumor metastasis in the liver.
自然杀伤 (NK) 和 NKT 细胞是抵御病原体和转化细胞的第一道防线。然而，它们功能的失调可能导致自身免疫性疾病。更好地了解控制 NK 和 NKT 效应功能的机制，应该会导致开发出许多疾病治疗的改进策略。应该考虑 NK 和 NKT 细胞所在的部位，因为越来越多的证据表明组织微环境强烈影响它们的功能。在这方面，肝脏是一个独特的免疫器官，其中对耐受性的需求与对病原体和组织损伤快速反应的能力之间的平衡受到严格调节。与其他器官相比，肝脏中的 NK 细胞具有增强的细胞溶解活性，这与肝相关 NK 细胞在作为抑制肝脏转移肿瘤的关键效应细胞中的作用一致。几项研究还表明，肝脏中的 NKT 细胞具有不同于其他器官的功能。虽然脾和胸腺 NKT 细胞已被证明可抑制糖尿病的发展、促进全身耐受的诱导，并受 IL-4 和其他 Th2 细胞因子的调节，但肝脏中某些 NKT 细胞亚群是 Th1 细胞因子（如干扰素 γ）的重要来源，是抗肿瘤反应的主要介导者。独特的特性和作为关键效应细胞的作用，使肝脏微环境中的 NK 和 NKT 细胞成为免疫治疗方法的有吸引力的目标，这些方法的目标是控制肝脏中的肿瘤转移。
