Bergamini Alberto, Chimenti Maria Sole, Baffari Eleonora, Guarino Maria Domenica, Gigliucci Gianfranco, Perricone Carlo, Perricone Roberto
Rheumatology, Allergology and Clinical Immunology, Department of Internal Medicine, Unit of Rheumatology, University of Rome Tor Vergata, Rome, Italy.
Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.
PLoS One. 2014 Mar 27;9(3):e92018. doi: 10.1371/journal.pone.0092018. eCollection 2014.
The immunoglobulin-like transcript-4 (ILT4) is an inhibitory receptor that modulates the activity of innate immune agents. We determined the expression of ILT4 and analysed the relationship with the expression of costimulatory proteins and tumor necrosis factor-α (TNF-α) production in monocytes from patients with psoriatic arthritis (PsA) starting anti-TNF treatment.
Peripheral blood monocytes from 15 healthy controls and from 16 patients with PsA were activated in vitro by CD40 ligand (CD40L) and analyzed for ILT4, CD40, CD80 and CD86 expression, and spontaneous lipopolysaccharide (LPS)-induced TNF-α production by flow cytometry, before and after treatment with adalimumab.
The percentage of ILT4-negative monocytes was greater in PsA patients compared to controls and negatively correlated with DAS44. Normal monocytes treated with sera of PsA patients showed a reduced expression of ILT4 compared with monocytes exposed to sera from controls. CD40, CD80 and CD86 expression was higher in patients compared to controls. Both spontaneous and LPS-induced TNF-α production was restricted to ILT4-negative monocytes and was greater in PsA patients compared to controls. Finally, twelve weeks-treatment with adalimumab resulted in a significant increase of ILT4 expression and a decrease of costimulatory molecules expression in PsA patients, compared to pre-therapy levels.
These data support the possibility that changes in the immunophenotype of monocytes play a role in the pathogenesis of PSA. Thus, modulation of the expression of ILT4 may represent an enticing new therapeutic target.
免疫球蛋白样转录物4（ILT4）是一种调节先天性免疫因子活性的抑制性受体。我们测定了银屑病关节炎（PsA）患者开始抗TNF治疗时单核细胞中ILT4的表达，并分析了其与共刺激蛋白表达及肿瘤坏死因子-α（TNF-α）产生之间的关系。
采用流式细胞术，对15名健康对照者和16名PsA患者的外周血单核细胞进行体外CD40配体（CD40L）激活，分析阿达木单抗治疗前后ILT4、CD40、CD80和CD86的表达，以及脂多糖（LPS）诱导的自发TNF-α产生情况。
与对照组相比，PsA患者中ILT4阴性单核细胞的百分比更高，且与疾病活动评分（DAS44）呈负相关。用PsA患者血清处理的正常单核细胞与用对照血清处理的单核细胞相比，ILT4表达降低。与对照组相比，患者的CD40、CD80和CD86表达更高。自发和LPS诱导的TNF-α产生均局限于ILT4阴性单核细胞，且PsA患者中的产生量高于对照组。最后，与治疗前水平相比，PsA患者接受12周阿达木单抗治疗后，ILT4表达显著增加，共刺激分子表达降低。
这些数据支持单核细胞免疫表型变化在PsA发病机制中起作用的可能性。因此，调节ILT4的表达可能是一个诱人的新治疗靶点。
