DNAM1 and TIGIT balance the T cell response, with low T cell TIGIT expression corresponding to inflammation in psoriatic disease

IF 4.1 Q2 IMMUNOLOGY
M. Jacobs, J. Pouw, M. O. Olde Nordkamp, T. Radstake, E. Leijten, M. Boes
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引用次数: 2

Abstract

Summary Objectives Signals at the contact site of antigen-presenting cells (APCs) and T cells help orchestrate the adaptive immune response. CD155 on APCs can interact with the stimulatory receptor DNAM1 or inhibitory receptor TIGIT on T cells. The CD155/DNAM1/TIGIT axis is under extensive investigation as immunotherapy target in inflammatory diseases including cancer, chronic infection and autoimmune diseases. We investigated a possible role for CD155/DNAM1/TIGIT signaling in psoriatic disease. Methods By flow cytometry, we analyzed peripheral blood mononuclear cells of patients with psoriasis (n = 20) or psoriatic arthritis (n = 21), and healthy individuals (n = 7). We measured CD155, TIGIT, and DNAM1 expression on leukocyte subsets and compared activation-induced cytokine production between CD155-positive and CD155-negative APCs. We assessed the effects of TIGIT and DNAM1 blockade on T cell activation, and related the expression of CD155/DNAM1/TIGIT axis molecules to measures of disease activity. Results High CD155 expression associates with tumor necrosis factor (TNF) production in myeloid and plasmacytoid dendritic cells (DC). In CD1c+ myeloid DC, activation-induced CD155 expression associates with increased HLA-DR expression. CD8 T cells – but not CD4 T cells – express high levels of TIGIT. DNAM1 blockade decreases T cell pro-inflammatory cytokine production, while TIGIT blockade increased T cell proliferation. Finally, T cell TIGIT expression shows an inverse correlation with inflammation biomarkers in psoriatic disease. Conclusion CD155 is increased on pro-inflammatory APCs, while the receptors DNAM1 and TIGIT expressed on T cells balance the inflammatory response by T cells. In psoriatic disease, low TIGIT expression on T cells is associated with systemic inflammation.
DNAM1和TIGIT平衡T细胞反应,银屑病中T细胞TIGIT低表达对应炎症
抗原呈递细胞(APCs)和T细胞接触部位的信号有助于协调适应性免疫反应。apc上的CD155可与T细胞上的刺激受体DNAM1或抑制受体TIGIT相互作用。CD155/DNAM1/TIGIT轴作为炎性疾病(包括癌症、慢性感染和自身免疫性疾病)的免疫治疗靶点正受到广泛的研究。我们研究了CD155/DNAM1/TIGIT信号在银屑病中的可能作用。方法采用流式细胞术对20例银屑病患者(n = 20)、21例银屑病关节炎患者(n = 21)和7例健康人的外周血单核细胞进行分析,检测CD155、TIGIT和DNAM1在白细胞亚群中的表达,并比较CD155阳性和CD155阴性apc活化诱导的细胞因子的产生。我们评估了TIGIT和DNAM1阻断对T细胞活化的影响,并将CD155/DNAM1/TIGIT轴分子的表达与疾病活动性的测量相关联。结果CD155高表达与髓细胞和浆细胞样树突状细胞(DC)肿瘤坏死因子(TNF)的产生有关。在CD1c+髓系DC中,活化诱导的CD155表达与HLA-DR表达增加相关。CD8 T细胞——而不是CD4 T细胞——表达高水平的TIGIT。DNAM1阻断减少T细胞促炎细胞因子的产生,而TIGIT阻断增加T细胞增殖。最后,银屑病中T细胞TIGIT表达与炎症生物标志物呈负相关。结论CD155在促炎APCs上表达增加,而T细胞上表达的受体DNAM1和TIGIT可平衡T细胞的炎症反应。在银屑病中,T细胞上TIGIT的低表达与全身性炎症有关。
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CiteScore
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