Natural Killer Cells: Potential Biomarkers and Therapeutic Target in Autoimmune Diseases?
Natural Killer Cells: Potential Biomarkers and Therapeutic Target in Autoimmune Diseases?
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DOI：
10.3389/fimmu.2021.616853
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发表时间：
2021
影响因子：
7.3
通讯作者：
Fierabracci A
中科院分区：
文献类型：
--
作者：
Gianchecchi E;Delfino DV;Fierabracci A
虽然自身免疫性疾病的确切发病机制仍未完全阐明，但它的发病机制是多因素的。在过去的几年里，自然杀伤(NK)细胞在塑造免疫反应中的作用得到了强调，尽管它们的参与与所涉及的亚群和发生这种相互作用的地点密切相关。NK细胞的数量和功能异常在几种不同的自身免疫性疾病中已有报道。在这篇综述中，我们报告了关于NK细胞参与全身和器官特异性自身免疫疾病的最新发现，包括1型糖尿病(T1D)、原发性胆管炎(PBC)、系统性硬化症、系统性红斑狼疮(SLE)、原发性Sjögren综合征、类风湿性关节炎和多发性硬化症。在T1D中，先天炎症诱导NK细胞激活，破坏Treg功能。此外，某些被确认为T1D危险因素的基因变异影响了NK细胞的激活，促进了它们的细胞毒活性。NK细胞在PBC的发病机制中的作用也被证实，PBC直接或间接地介导胆管上皮细胞的破坏。患者外周血和肝脏中NK细胞的频率和数量均增加，并与NK细胞的细胞毒活性和穿孔素表达水平增加有关。在抗原提呈细胞存在的情况下，NK细胞也通过自身反应性的CD4T细胞激活参与了疾病的延续。在系统性硬化症(SSC)中，除了表型异常外，患者还表现出CD56hi NK细胞减少。此外，NK细胞缺乏杀伤活性。研究了激活和抑制杀伤细胞免疫球蛋白样受体(KIRS)在系统性红斑狼疮(SSC)和系统性红斑狼疮易感性中的作用。此外，在不同的全身性自身免疫条件下，已经发现了针对KIRS的自身抗体。由于NK亚群在调节免疫介导的病理过程中的作用，它可能是疾病活动的潜在标记物和治疗干预的靶点。
Autoimmune diseases recognize a multifactorial pathogenesis, although the exact mechanism responsible for their onset remains to be fully elucidated. Over the past few years, the role of natural killer (NK) cells in shaping immune responses has been highlighted even though their involvement is profoundly linked to the subpopulation involved and to the site where such interaction takes place. The aberrant number and functionality of NK cells have been reported in several different autoimmune disorders. In the present review, we report the most recent findings regarding the involvement of NK cells in both systemic and organ-specific autoimmune diseases, including type 1 diabetes (T1D), primary biliary cholangitis (PBC), systemic sclerosis, systemic lupus erythematosus (SLE), primary Sjögren syndrome, rheumatoid arthritis, and multiple sclerosis. In T1D, innate inflammation induces NK cell activation, disrupting the Treg function. In addition, certain genetic variants identified as risk factors for T1D influenced the activation of NK cells promoting their cytotoxic activity. The role of NK cells has also been demonstrated in the pathogenesis of PBC mediating direct or indirect biliary epithelial cell destruction. NK cell frequency and number were enhanced in both the peripheral blood and the liver of patients and associated with increased NK cell cytotoxic activity and perforin expression levels. NK cells were also involved in the perpetuation of disease through autoreactive CD4 T cell activation in the presence of antigen-presenting cells. In systemic sclerosis (SSc), in addition to phenotypic abnormalities, patients presented a reduction in CD56hi NK-cells. Moreover, NK cells presented a deficient killing activity. The influence of the activating and inhibitory killer cell immunoglobulin-like receptors (KIRs) has been investigated in SSc and SLE susceptibility. Furthermore, autoantibodies to KIRs have been identified in different systemic autoimmune conditions. Because of its role in modulating the immune-mediated pathology, NK subpopulation could represent a potential marker for disease activity and target for therapeutic intervention.
影响因子：
2.3
作者：
Majorczyk E;Pawlik A;Gendosz D;Kuśnierczyk P
通讯作者：
Kuśnierczyk P