1 Baylor College of Medicine , Houston, Texas.
2 Shire, Lexington, Massachusetts.
J Ocul Pharmacol Ther. 2017 Jan/Feb;33(1):5-12. doi: 10.1089/jop.2016.0105. Epub 2016 Dec 1.
Dry eye disease (DED) is a common ocular disorder associated with inflammation of the lacrimal gland and ocular surface. The interaction of the integrin lymphocyte function-associated antigen-1 (LFA-1) with its cognate ligand intercellular adhesion molecule-1 (ICAM-1) is known to have important roles in the interaction of a variety of cells involved in immune responses and inflammation, including those prominent in ocular surface inflammation. Lifitegrast, an LFA-1 antagonist that blocks binding of ICAM-1 to LFA-1, has recently been approved in the United States for the treatment of signs and symptoms of DED. In this review, we evaluate research findings to explore the potential role of LFA-1/ICAM-1 interaction in the pathophysiology of DED, and the evidence supporting LFA-1/ICAM-1 interaction as a rational therapeutic target in DED. The results of our review suggest that LFA-1/ICAM-1 interaction may play important roles in the cell-mediated immune response and inflammation associated with DED, including facilitating the homing of dendritic cells to the lymph nodes, interaction of dendritic cells with T cells and subsequent T cell activation/differentiation, migration of activated CD4 T cells from the lymph nodes to the ocular surface, reactivation of T cells by resident antigen-presenting cells at the ocular surface, and recruitment and retention of LFA-1-expressing T cells in the conjunctival epithelium. Based on the available evidence, inhibition of LFA-1/ICAM-1 interaction represents a rational targeted approach in treating DED. Notably, inhibition of LFA-1/ICAM-1 binding with lifitegrast offers a novel approach to reducing ocular surface inflammation in this condition.
干眼症（DED）是一种常见的眼部疾病，与泪腺和眼表面炎症有关。整合素淋巴细胞功能相关抗原-1（LFA-1）与其同源配体细胞间黏附分子-1（ICAM-1）的相互作用，已知在各种参与免疫反应和炎症的细胞相互作用中具有重要作用，包括在眼表面炎症中起重要作用的细胞。LFA-1 拮抗剂 lifitegrast 可阻止 ICAM-1 与 LFA-1 的结合，最近已被批准用于治疗 DED 的体征和症状。在这篇综述中，我们评估了研究结果，以探讨 LFA-1/ICAM-1 相互作用在 DED 病理生理学中的潜在作用，以及支持 LFA-1/ICAM-1 相互作用作为 DED 合理治疗靶点的证据。我们的综述结果表明，LFA-1/ICAM-1 相互作用可能在与 DED 相关的细胞介导免疫反应和炎症中发挥重要作用，包括促进树突状细胞向淋巴结归巢、树突状细胞与 T 细胞的相互作用以及随后的 T 细胞激活/分化、活化的 CD4 T 细胞从淋巴结向眼表面的迁移、驻留在眼表面的抗原呈递细胞重新激活 T 细胞，以及 LFA-1 表达 T 细胞在结膜上皮中的募集和保留。基于现有证据，抑制 LFA-1/ICAM-1 相互作用代表了治疗 DED 的一种合理的靶向方法。值得注意的是，lifitegrast 抑制 LFA-1/ICAM-1 结合为减少这种情况下的眼表面炎症提供了一种新方法。
