Immunoregulatory Role of NK Cells in Tissue Inflammation and Regeneration.
Immunoregulatory Role of NK Cells in Tissue Inflammation and Regeneration.
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DOI：
10.3389/fimmu.2017.00301
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发表时间：
2017
影响因子：
7.3
通讯作者：
Hahn YS
中科院分区：
文献类型：
--
作者：
Tosello-Trampont A;Surette FA;Ewald SE;Hahn YS
NK细胞是抵抗病毒感染和癌症的重要第一道防线，也参与组织稳态。过去十年中对NK细胞活化的研究表明，它们能够对组织损伤引起的炎症刺激做出反应，并有助于疾病的进展和解决。通过免疫效应细胞之间的相互作用的炎症反应的加剧促进非酒精性脂肪性肝病（NAFLD）进展为脂肪变性、肝硬化和肝细胞癌（HCC）。当发生肝损伤时，巨噬细胞活化对于启动与肝脏中存在的邻近细胞（包括肝细胞和NK细胞）的串扰至关重要，并且这种相互作用在塑造肝脏疾病中的免疫应答中的重要性越来越被认识到。所造成的结构损伤可以通过自限性纤维化过程部分再生，尽管持续性肝损伤将导致慢性纤维化和组织组织和功能的丧失。NK细胞的细胞毒活性在诱导肝星状细胞凋亡从而抑制肝纤维化进展中起重要作用。或者，在某些疾病中，例如肝癌，NK细胞可能会失调，从而促进免疫抑制状态，使肿瘤能够逃脱免疫监视。本文综述了目前对NK细胞对组织炎症和代谢性肝病的贡献的认识，以及开发针对NK细胞免疫调节功能的治疗方法的持续努力。
NK cells represent an important first line of defense against viral infection and cancer and are also involved in tissue homeostasis. Studies of NK cell activation in the last decade have revealed that they are able to respond to the inflammatory stimuli evoked by tissue damage and contribute to both progression and resolution of diseases. Exacerbation of the inflammatory response through interactions between immune effector cells facilitates the progression of non-alcoholic fatty liver disease (NAFLD) into steatosis, cirrhosis, and hepatocellular carcinoma (HCC). When hepatic damage is incurred, macrophage activation is crucial for initiating cross talk with neighboring cells present in the liver, including hepatocytes and NK cells, and the importance of this interaction in shaping the immune response in liver disease is increasingly recognized. Inflicted structural damage can be in part regenerated via the process of self-limiting fibrosis, though persistent hepatic damage will lead to chronic fibrosis and loss of tissue organization and function. The cytotoxic activity of NK cells plays an important role in inducing hepatic stellate cell apoptosis and thus curtailing the progression of fibrosis. Alternatively, in some diseases, such as HCC, NK cells may become dysregulated, promoting an immunosuppressive state where tumors are able to escape immune surveillance. This review describes the current understanding of the contributions of NK cells to tissue inflammation and metabolic liver diseases and the ongoing effort to develop therapeutics that target the immunoregulatory function of NK cells.