CD4+LAG-3+ T cells are decreased in active psoriatic arthritis patients and their restoration in vitro is mediated by TNF inhibitors
CD4+LAG-3+ T cells are decreased in active psoriatic arthritis patients and their restoration in vitro is mediated by TNF inhibitors
复制标题
DOI：
10.1111/cei.13646
复制
发表时间：
2021-08-05
影响因子：
4.6
通讯作者：
Elkayam, Ori
中科院分区：
文献类型：
--
作者：
Gertel, Smadar;Polachek, Ari;Elkayam, Ori
银屑病关节炎（PsA）是一种与T细胞失调相关的慢性炎症性疾病。淋巴细胞活化基因(LAG)-3是以可溶性形式在T细胞上表达的调节受体之一。体外分析了LAG-3在疾病活动性最小（MDA）、活动性疾病（非MDA）和健康对照组PsA患者T细胞上的表达。在体外培养的外周血单个核细胞（PBMCs）中，CD4(+) T细胞上LAG-3的表达在MDA PsA患者（7.5 +/- 0.9）（n = 14）和健康对照（7.8 +/- 0.6）（n = 15）中相似，而在非MDA PsA患者（3.1 +/- 0.3）（n = 13）中显著降低（p < 0.0001）。体外观察到PsA临床疾病活动性与%CD4(+)LAG-3(+) T细胞呈负相关（银屑病综合活动性指数r = -0.47, p < 0.02，银屑病关节炎疾病活动性评分r = -0.51, p < 0.008）。CD4(+) T细胞与抗肿瘤坏死因子（TNF）或抗白细胞介素(IL)-17A体外共培养对MDA - PsA患者和健康对照中LAG-3（+）的表达无影响。在非mda患者中，抗tnf而非抗il - 17a可恢复%CD4(+)LAG-3(+) T细胞（分别为7.9 +/- 0.9和3.2 +/- 0.4）（p < 0.0004）。与健康对照（n = 35）相比，未发生生物PsA的患者（n = 39）血清中可溶性LAG-3水平较低（p < 0.03）。CD4(+) T细胞的LAG-3受损可能反映了PsA疾病的活跃状态。抗tnf在体外具有上调CD4(+)LAG-3(+) T细胞的作用。
Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with T cell dysregulation. The lymphocyte-activation gene (LAG)-3 is one of the regulatory receptors expressed on T cells in a soluble form. LAG-3 expression on T cells was analyzed in vitro in PsA patients with minimal disease activity (MDA), active disease (non-MDA) and healthy controls. In cultured in-vitro peripheral blood mononuclear cells (PBMCs), LAG-3 expression on CD4(+) T cells was similar in both MDA PsA patients (7.5 +/- 0.9) (n = 14) and healthy controls (7.8 +/- 0.6) (n = 15), but significantly lower in non-MDA PsA patients (3.1 +/- 0.3) (n = 13) (p < 0.0001). An inverse correlation between PsA clinical disease activity and %CD4(+)LAG-3(+) T cells in vitro was observed (composite psoriatic disease activity index r = -0.47, p < 0.02 and psoriatic arthritis disease activity score, r = -0.51, p < 0.008). In-vitro co-culture of CD4(+) T cells with anti-tumor necrosis factor (TNF) or anti-interleukin (IL)-17A had no effect on LAG-3(+) expression in MDA PsA patients and healthy controls. In non-MDA patients, anti-TNF, but not anti-IL-17A, restored the %CD4(+)LAG-3(+) T cells (7.9 +/- 0.9 and 3.2 +/- 0.4, respectively) (p < 0.0004). Lower soluble LAG-3 levels were found in sera of naive to biological PsA patients (n = 39) compared to healthy controls (n = 35) (p < 0.03). Impaired LAG-3 on CD4(+) T cells may reflect active PsA disease state. Anti-TNFs have potency to up-regulate the CD4(+)LAG-3(+) T cells in vitro.