Faculty of Medicine and Health Sciences, Department of Rheumatology, Laboratory for Molecular Immunology and Inflammation, Ghent University Hospital, , Ghent, Belgium.
Ann Rheum Dis. 2014 Jun;73(6):1223-31. doi: 10.1136/annrheumdis-2013-203881. Epub 2013 Jun 5.
Killer cell lectin-like receptor G1 (KLRG1) is an NK cell marker also expressed on T cells showing an immunosenescent phenotype. KLRG1 binding to its ligand E-cadherin inhibits functional responses. It was recently shown that soluble E-cadherin (sE-cadherin) also influences KLRG1 signalling, although its involvement in arthritis is unknown. Our goal was to evaluate the contribution of KLRG1(+) T cells to synovitis.
Paired peripheral blood (PB) and synovial fluid (SF) mononuclear cells from 21 patients with spondyloarthritis (SpA) or rheumatoid arthritis (RA), eight with crystal-induced arthritis and 10 controls were obtained. T cells were characterised for KLRG1 expression directly ex vivo, while TNF-α/IFN-γ production was assessed after polyclonal stimulation. Assays of chemotaxis response towards SF were conducted. Additionally, sE-cadherin levels in our paired samples were determined. Moreover, TNF-α/IFN-γ production by antigen-specific T cells was evaluated in the presence of sE-cadherin.
KLRG1(+) T cells were enriched in SF as opposed to PB of SpA and RA patients, which contrasts with results obtained in crystal-induced arthritides. KLRG1(+) T cells were more functionally active as opposed to KLRG1(-) T cells and migrated preferentially towards SpA and RA SF. sE-cadherin levels were higher in SF versus plasma. The presence of sE-cadherin enhanced the number of KLRG1(+) CD4(+) T cells able to produce TNF-α but not IFN-γ.
sE-cadherin contributes to the local proinflammatory environment in the joint by favouring TNF-α production by KLRG1(+) CD4(+) T cells. This pathway seems to be operational in both SpA and RA, but not in crystal-induced arthritis.
杀伤细胞凝集素样受体 G1（KLRG1）是一种 NK 细胞标志物，也表达在表现出免疫衰老表型的 T 细胞上。KLRG1 与它的配体 E-钙黏蛋白结合抑制功能反应。最近表明，可溶性 E-钙黏蛋白（sE-cadherin）也影响 KLRG1 信号转导，尽管其在关节炎中的作用尚不清楚。我们的目标是评估 KLRG1(+)T 细胞对滑膜炎的贡献。
从 21 例强直性脊柱炎（SpA）或类风湿关节炎（RA）患者、8 例晶体诱导性关节炎患者和 10 例对照者的外周血（PB）和滑液（SF）单核细胞中获得配对样本。T 细胞在体外直接进行 KLRG1 表达的特征分析，同时评估多克隆刺激后 TNF-α/IFN-γ 的产生。进行趋化反应对 SF 的测定。此外，我们还在配对样本中测定 sE-cadherin 的水平。此外，还评估了 sE-cadherin 存在时抗原特异性 T 细胞的 TNF-α/IFN-γ 产生。
与晶体诱导性关节炎患者的结果相反，KLRG1(+)T 细胞在 SpA 和 RA 患者的 SF 中富集，而在 PB 中则较少。与 KLRG1(-)T 细胞相比，KLRG1(+)T 细胞的功能更为活跃，并且更倾向于向 SpA 和 RA SF 迁移。sE-cadherin 在 SF 中的水平高于血浆。sE-cadherin 的存在增强了能够产生 TNF-α但不能产生 IFN-γ的 KLRG1(+)CD4(+)T 细胞的数量。
sE-cadherin 通过促进 KLRG1(+)CD4(+)T 细胞产生 TNF-α来促进关节局部炎症环境。该途径在 SpA 和 RA 中起作用，但在晶体诱导性关节炎中不起作用。
