Table1_The Tipped Balance of ILC1/ILC2 in Peripheral Blood of Oral Lichen Planus Is Related to Inflammatory Cytokines.DOCX

Oral lichen planus (OLP) is an immune-inflammatory disease mediated by T cells. Innate lymphoid cells (ILCs) constitute a novel family of immune cells that initially originate from common innate lymphoid progenitors. Termed “T cells counterparts,” ILCs play a prominent role in inflammatory-immune diseases. However, the characterization of ILCs and their related induced factors were unclear in OLP. In the present study, the phenotypic characteristics of ILCs and their correlation with inflammatory cytokines were explored in the peripheral blood of OLP patients and healthy controls. We found that the proportion of total ILCs was expanded in OLP and was positively correlated with disease severity. The highly skewed distribution of ILC subpopulations was notable in OLP. Specifically, the frequency of ILC1s was significantly increased, while that of ILC2s was significantly reduced in total ILCs of OLP, resulting in the markedly elevated ILC1/ILC2 ratio in OLP. Correspondingly, ILCs in OLP displayed high expression of T-bet but low expression of GATA3. In addition, the IFN-γ expression level was elevated in ILC1s, whereas the IL-4 expression level was decreased in ILC2s. Moreover, ILC-associated activators IL-12, IL-18, and IL-1β were upregulated in OLP plasma, with IL-12 and IL-1β both positively correlated with the ILC1/ILC2 ratio. Further in vitro stimulation tests indicated that OLP plasma remarkedly increased the ILC1/ILC2 ratio, especially that IL-12 and IL-1β tipped the balance between ILC1s and ILC2s toward ILC1s in total ILCs. Overall, elevated levels of IL-12 and IL-1β might act as environmental cues in tipping the balance of ILC1/ILC2 in the peripheral blood of OLP, contributing to the immune dysregulation in OLP.

口腔扁平苔藓（oral lichen planus, OLP）是一种由T细胞介导的免疫炎症性疾病。固有淋巴样细胞（innate lymphoid cells, ILCs）是一类新近发现的免疫细胞家族，其起源于共同固有淋巴样祖细胞，被称为“T细胞类似物”，在炎症免疫性疾病中发挥关键作用。然而，目前针对OLP中ILCs的特征及其相关诱导因子的研究仍不明确。本研究通过分析OLP患者与健康对照的外周血样本，探讨了ILCs的表型特征及其与炎症细胞因子的相关性。研究结果显示，OLP患者外周血中总ILCs的比例显著升高，且与疾病严重程度呈正相关。OLP患者体内ILC亚群的分布呈现显著偏倚。具体而言，在总ILCs中，OLP患者的ILC1频率显著升高，而ILC2频率显著降低，致使OLP患者体内ILC1/ILC2比值明显升高。相应地，OLP患者体内的ILCs高表达T-bet，低表达GATA3。此外，ILC1中干扰素-γ（interferon-gamma, IFN-γ）的表达水平升高，而ILC2中白细胞介素-4（interleukin-4, IL-4）的表达水平降低。另外，OLP患者血浆中ILC相关激活因子白细胞介素-12（interleukin-12, IL-12）、白细胞介素-18（interleukin-18, IL-18）及白细胞介素-1β（interleukin-1β, IL-1β）均表达上调，其中IL-12与IL-1β均与ILC1/ILC2比值呈正相关。进一步的体外刺激实验表明，OLP患者血浆可显著升高ILC1/ILC2比值，其中IL-12与IL-1β可使总ILCs中ILC1与ILC2的平衡向ILC1倾斜。综上，升高的IL-12与IL-1β水平可作为环境信号，使OLP患者外周血中ILC1/ILC2的平衡发生偏移，进而参与OLP的免疫失调过程。