Skejoe Caecilie, Hansen Aida S, Stengaard-Pedersen Kristian, Junker Peter, Hoerslev-Pedersen Kim, Hetland Merete L, Oestergaard Mikkel, Greisen Stinne, Hvid Malene, Deleuran Mette, Deleuran Bent
Department of Biomedicine, Aarhus University Denmark.
Department of Rheumatology, Aarhus University Hospital Denmark.
Am J Clin Exp Immunol. 2022 Jun 15;11(3):34-44. eCollection 2022.
Rheumatoid arthritis (RA) is a chronic autoimmune disease, that involves both pro- and anti-inflammatory mechanisms. The purpose of the present study is to investigate T-cell immunoglobulin and mucin domain 3 (Tim-3) in RA.
Plasma levels of soluble (s) Tim-3 in early RA (n=98), were followed, to evaluate association with treatment and disease activity, acquired from a prospective collected biobank (clinicaltrials.gov (NCT00660647)). We also investigate the influence of Tim-3 on spontaneous cytokine production in synovial fluid mononuclear cells (SFMC) from RA patients after addition of neutralizing anti-Tim-3's antibodies, either alone or in combination with neutralizing anti-Programmed Cell death protein 1 (PD-1) antibodies.
Long-time stimulated CD4 T-cells expressed high levels of Tim-3, but tended to decrease their PD-1 expression. Tim-3 expression was exclusively seen co-expressed with PD-1 by CD3, CD4, CD45RO positive cells in the inflamed RA joint. Addition of neutralizing Tim-3 antibodies increased the secretion of IFNγ and MCP-1, in SFMC cultures from RA. Whereas neutralizing anti-PD-1 antibodies showed a broader impact on cytokine production. Finally, we observed that soluble Tim-3 is increased in plasma and is associated with disease activity in early RA.
Taken together, our findings indicate disease-suppressive functions of Tim-3 in RA.
类风湿关节炎（RA）是一种慢性自身免疫性疾病，涉及促炎和抗炎机制。本研究的目的是调查RA中的T细胞免疫球蛋白和粘蛋白结构域3（Tim-3）。
对早期RA患者（n = 98）血浆中可溶性（s）Tim-3水平进行跟踪，以评估其与治疗及疾病活动度的相关性，数据来自前瞻性收集的生物样本库（clinicaltrials.gov（NCT00660647））。我们还研究了在添加中和性抗Tim-3抗体单独或与中和性抗程序性细胞死亡蛋白1（PD-1）抗体联合使用后，Tim-3对RA患者滑膜液单核细胞（SFMC）中细胞因子自发产生的影响。
长期刺激的CD4 T细胞表达高水平的Tim-3，但PD-1表达趋于降低。在炎症性RA关节中，Tim-3表达仅见于CD3、CD4、CD45RO阳性细胞与PD-1共表达。添加中和性Tim-3抗体可增加RA患者SFMC培养物中IFNγ和MCP-1的分泌。而中和性抗PD-1抗体对细胞因子产生的影响更广泛。最后，我们观察到早期RA患者血浆中可溶性Tim-3升高，且与疾病活动度相关。
综上所述，我们的研究结果表明Tim-3在RA中具有疾病抑制功能。
