The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel-Canada of the Faculty of Medicine (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.
The Internal medicine department and the Rheumatology unit, Hadassah Medical Center, Jerusalem, 91120, Israel.
Sci Rep. 2019 Feb 4;9(1):1351. doi: 10.1038/s41598-018-37448-z.
Rheumatoid Arthritis (RA) causes chronic inflammation of joints. The cytokines TNFα and IFNγ are central players in RA, however their source has not been fully elucidated. Natural Killer (NK) cells are best known for their role in elimination of viral-infected and transformed cells, and they secrete pro-inflammatory cytokines. NK cells are present in the synovial fluids (SFs) of RA patients and are considered to be important in bone destruction. However, the phenotype and function of NK cells in the SFs of patients with erosive deformative RA (DRA) versus non-deformative RA (NDRA) is poorly characterized. Here we characterize the NK cell populations present in the blood and SFs of DRA and NDRA patients. We demonstrate that a distinct population of activated synovial fluid NK (sfNK) cells constitutes a large proportion of immune cells found in the SFs of DRA patients. We discovered that although sfNK cells in both DRA and NDRA patients have similar phenotypes, they function differently. The DRA sfNK secrete more TNFα and IFNγ upon exposure to IL-2 and IL-15. Consequently, we suggest that sfNK cells may be a marker for more severely destructive RA disease.
类风湿关节炎（RA）会导致关节慢性炎症。细胞因子 TNFα 和 IFNγ 是 RA 的核心参与者，但其来源尚未完全阐明。自然杀伤（NK）细胞以其在消除病毒感染和转化细胞方面的作用而闻名，它们会分泌促炎细胞因子。NK 细胞存在于 RA 患者的滑膜液（SFs）中，被认为在骨破坏中很重要。然而，侵蚀性变形性 RA（DRA）与非变形性 RA（NDRA）患者 SFs 中的 NK 细胞表型和功能特征描述甚少。在这里，我们描述了 DRA 和 NDRA 患者血液和 SF 中存在的 NK 细胞群体。我们证明，一种独特的活化滑膜液 NK（sfNK）细胞群体构成了 DRA 患者 SFs 中发现的大量免疫细胞。我们发现，尽管 DRA 和 NDRA 患者的 sfNK 细胞具有相似的表型，但它们的功能不同。DRA sfNK 在暴露于 IL-2 和 IL-15 时会分泌更多的 TNFα 和 IFNγ。因此，我们认为 sfNK 细胞可能是更严重破坏性 RA 疾病的标志物。
