Park Ki-Jeong, Kim Tae-Ok, Cho Young-Nan, Jin Hye-Mi, Jo Young-Goun, Shin Hong-Joon, Kho Bo Gun, Kee Seung-Jung, Park Yong-Wook
Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
Department of Pulmonology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
Front Immunol. 2024 Aug 30;15:1433028. doi: 10.3389/fimmu.2024.1433028. eCollection 2024.
Acute respiratory distress syndrome (ARDS) presents a global health challenge, characterized by significant morbidity and mortality. However, the role of natural killer T (NKT) cells in human ARDS remains poorly understood. Therefore, this study explored the numerical and functional status of NKT cells in patients with ARDS, examining their clinical relevance and interactions with macrophages and fibroblasts during various stages of the syndrome.
Peripheral blood from 40 ARDS patients and 30 healthy controls was analyzed, with paired samples of peripheral blood and bronchoalveolar lavage fluid (BALF) from seven ARDS patients. We measured levels of NKT cells, cytokines, CD69, programmed death-1 (PD-1), and annexin-V using flow cytometry, and extracellular matrix (ECM) protein expression using real-time PCR.
ARDS patients exhibited decreased circulating NKT cells with elevated CD69 expression and enhanced IL-17 production. The reduction in NKT cells correlated with PaO/FiO ratio, albumin, and C-reactive protein levels. Proliferative responses to α-galactosylceramide (α-GalCer) were impaired, and co-culturing NKT cells with monocytes or T cells from ARDS patients resulted in a reduced α-GalCer response. Increased and activated NKT cells in BALF induced proinflammatory cytokine release by macrophages and ECM protein expression in fibroblasts.
ARDS is associated with a numerical deficiency but functional activation of circulating NKT cells, showing impaired responses to α-GalCer and altered interactions with immune cells. The increase in NKT cells within BALF suggests their role in inducing inflammation and remodeling/fibrosis, highlighting the potential of targeting NKT cells as a therapeutic approach for ARDS.
急性呼吸窘迫综合征（ARDS）是一项全球性的健康挑战，具有较高的发病率和死亡率。然而，自然杀伤T（NKT）细胞在人类ARDS中的作用仍知之甚少。因此，本研究探讨了ARDS患者中NKT细胞的数量和功能状态，研究其在该综合征不同阶段的临床相关性以及与巨噬细胞和成纤维细胞的相互作用。
分析了40例ARDS患者和30例健康对照者的外周血，并采集了7例ARDS患者的外周血和支气管肺泡灌洗液（BALF）配对样本。我们使用流式细胞术测量了NKT细胞、细胞因子、CD69、程序性死亡1（PD-1）和膜联蛋白V的水平，并使用实时PCR检测了细胞外基质（ECM）蛋白表达。
ARDS患者循环中的NKT细胞减少，CD69表达升高，IL-17产生增加。NKT细胞的减少与PaO/FiO比值、白蛋白和C反应蛋白水平相关。对α-半乳糖神经酰胺（α-GalCer）的增殖反应受损，将ARDS患者的NKT细胞与单核细胞或T细胞共培养会导致α-GalCer反应降低。BALF中NKT细胞的增加和激活诱导了巨噬细胞释放促炎细胞因子和成纤维细胞中ECM蛋白的表达。
ARDS与循环中NKT细胞数量不足但功能激活有关，表现为对α-GalCer反应受损以及与免疫细胞的相互作用改变。BALF中NKT细胞的增加表明它们在诱导炎症和重塑/纤维化中的作用，突出了将NKT细胞作为ARDS治疗方法的潜力。
