Laboratory of Innate Immunity, University of Montreal, Montreal, Quebec, Canada.
CHU Sainte-Justine Research Center, University of Montreal, Montreal, Quebec, Canada.
Mediators Inflamm. 2020 Feb 19;2020:6401969. doi: 10.1155/2020/6401969. eCollection 2020.
We investigated activation status, cytotoxic potential, and gut homing ability of the peripheral blood Natural Killer (NK) cells in Crohn disease (CD) patients. For this purpose, we compared the expression of different activating and inhibitory receptors (KIR and non-KIR) and integrins on NK cells as well as their recent degranulation history between the patients and age-matched healthy controls. The study was conducted using freshly obtained peripheral blood samples from the study participants. Multiple color flow cytometry was used for these determinations. Our results show that NK cells from treatment-naïve CD patients expressed higher levels of activating KIR as well as other non-KIR activating receptors vis-à-vis healthy controls. They also showed increased frequencies of the cells expressing these receptors. The expression of several KIR and non-KIR inhibitory receptors tended to decrease compared with the cells from healthy donors. NK cells from the patients also expressed increased levels of different gut-homing integrin molecules and showed a history of increased recent degranulation events both constitutively and in response to their in vitro stimulation. Furthermore, treatment of the patients tended to reverse these NK cell changes. Our results demonstrate unequivocally, for the first time, that peripheral blood NK cells in treatment-naïve CD patients are more activated and are more poised to migrate to the gut compared to their counterpart cells from healthy individuals. Moreover, they show that treatment of the patients tends to normalize their NK cells. The results suggest that NK cells are very likely to play a role in the immunopathogenesis of Crohn disease.
我们研究了克罗恩病（CD）患者外周血自然杀伤（NK）细胞的激活状态、细胞毒性潜力和肠道归巢能力。为此，我们比较了患者和年龄匹配的健康对照者 NK 细胞上不同激活和抑制受体（KIR 和非 KIR）和整合素的表达以及它们最近的脱颗粒史。这项研究使用研究参与者的新鲜外周血样本进行。使用多色流式细胞术进行这些测定。我们的结果表明，与健康对照者相比，未经治疗的 CD 患者的 NK 细胞表达更高水平的激活 KIR 以及其他非 KIR 激活受体。它们还显示出表达这些受体的细胞的频率增加。与来自健康供体的细胞相比，几种 KIR 和非 KIR 抑制受体的表达趋于减少。患者的 NK 细胞还表达不同的肠道归巢整合素分子的水平增加，并表现出固有和体外刺激后脱颗粒事件增加的历史。此外，患者的治疗倾向于逆转这些 NK 细胞变化。我们的结果首次明确表明，与健康个体的对应细胞相比，未经治疗的 CD 患者外周血 NK 细胞更活跃，并且更有可能迁移到肠道。此外，它们表明患者的治疗倾向于使他们的 NK 细胞正常化。结果表明 NK 细胞很可能在克罗恩病的免疫发病机制中发挥作用。
