Gelmez Metin Yusuf, Cinar Suzan, Cetin Esin Aktas, Ozcit-Gürel Gulce, Babuna-Kobaner Goncagul, Erdugan Murat, Gul Ahmet, Akdag-Kose Afet, Deniz Gunnur
Department of Immunology, Aziz Sancar Institute of Experimental Medicine (Aziz Sancar DETAE), Istanbul University, Istanbul, Turkey.
Department of Dermatology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Immunol Lett. 2021 Jul;235:1-8. doi: 10.1016/j.imlet.2021.04.008. Epub 2021 Apr 23.
Innate lymphoid cells (ILCs) are lymphoid cells that have important effector and regulatory functions in innate immunity and tissue remodeling. Uncontrolled activation and proliferation of ILCs can contribute to inflammatory autoimmune diseases. Behcet's disease (BD) is a complex systemic inflammatory disorder of unknown etiology. It has been shown that natural killer (NK) cells may play an immunoregulatory role in BD, however the role of ILCs is unknown. In this study, the levels and functions of ILCs and NK cell subsets in BD patients were investigated. Cell surface and cytotoxic granules (perforin and granzyme) expression of NK cells and ILCs were evaluated and labeled according to whole blood lysing protocol in peripheral blood samples obtained from the patients and healthy subjects. Cytokine levels of NK cells were investigated in stimulated peripheral blood mononuclear cells. All data were analyzed by flow cytometry. Total ILC and ILC3 cells were increased in active BD patients compared to inactive BD patients and healthy subjects. There was no significant difference between the patients and healthy subjects regarding NK cell surface and intracellular molecule expression. Although, an increase in IFN-γ and IL-17, and a decrease in IL-4 levels were observed in CD56 NK cell subset of BD patients. Recent studies showed increased neutrophilic infiltration and IL-17 secreting Th17 cells in BD patients. It is known that ILC3cells are similar to Th17 subset regarding their cytokine profile and transcription factor expression patterns. Results of current study may suggest that inflammatory microenvironment in BD patients might direct ILC cells to differentiate into ILC3 subset, and IL-17 released by NK cells might have a role in neutrophilic infiltration.
固有淋巴细胞（ILCs）是在固有免疫和组织重塑中具有重要效应和调节功能的淋巴细胞。ILCs的不受控制的激活和增殖可导致炎症性自身免疫疾病。白塞病（BD）是一种病因不明的复杂全身性炎症性疾病。已有研究表明自然杀伤（NK）细胞可能在BD中发挥免疫调节作用，然而ILCs的作用尚不清楚。在本研究中，对BD患者中ILCs和NK细胞亚群的水平及功能进行了研究。根据全血裂解方案，对从患者和健康受试者获取的外周血样本中的NK细胞和ILCs的细胞表面及细胞毒性颗粒（穿孔素和颗粒酶）表达进行评估和标记。在刺激的外周血单个核细胞中研究NK细胞的细胞因子水平。所有数据均通过流式细胞术进行分析。与非活动期BD患者和健康受试者相比，活动期BD患者的总ILC和ILC3细胞增加。患者与健康受试者在NK细胞表面和细胞内分子表达方面无显著差异。尽管在BD患者的CD56 NK细胞亚群中观察到IFN-γ和IL-17增加，IL-4水平降低。最近的研究表明BD患者中嗜中性粒细胞浸润增加以及分泌IL-17的Th17细胞增加。已知ILC3细胞在细胞因子谱和转录因子表达模式方面与Th17亚群相似。本研究结果可能提示BD患者的炎症微环境可能引导ILC细胞分化为ILC3亚群，并且NK细胞释放的IL-17可能在嗜中性粒细胞浸润中起作用。
