Department of Biological Hematology, CHU Montpellier, 34295 Montpellier, France.
Department of Clinical Hematology, CHU Montpellier, 34295 Montpellier, France.
Int J Mol Sci. 2022 Dec 17;23(24):16136. doi: 10.3390/ijms232416136.
Leukocyte-associated immunoglobulin (Ig)-like receptor 1 (LAIR1, CD305) belongs to the family of immune-inhibitory receptors and is widely expressed on hematopoietic mature cells, particularly on immune cells. Four different types of ligands of LAIR1 have been described, including collagens, suggesting a potential immune-regulatory function on the extracellular matrix. By modulating cytokine secretion and cellular functions, LAIR1 displays distinct patterns of expression among NK cell and T/B lymphocyte subsets during their differentiation and cellular activation and plays a major negative immunoregulatory role. Beyond its implications in physiology, the activity of LAIR1 can be inappropriately involved in various autoimmune or inflammatory disorders and has been implicated in cancer physiopathology, including hematological neoplasms. Its action as an inhibitory receptor can result in the dysregulation of immune cellular responses and in immune escape within the tumor microenvironment. Furthermore, when expressed by tumor cells, LAIR1 can modulate their proliferation or invasion properties, with contradictory pro- or anti-tumoral effects depending on tumor type. In this review, we will focus on its role in normal physiological conditions, as well as during pathological situations, including hematological malignancies. We will also discuss potential therapeutic strategies targeting LAIR1 for the treatment of various autoimmune diseases and cancer settings.
白细胞相关免疫球蛋白样受体 1(LAIR1,CD305)属于免疫抑制受体家族,广泛表达于造血成熟细胞,尤其是免疫细胞。LAIR1 有四种不同类型的配体,包括胶原,提示其在外基质中可能具有免疫调节功能。LAIR1 通过调节细胞因子分泌和细胞功能,在 NK 细胞和 T/B 淋巴细胞亚群的分化和细胞激活过程中表现出不同的表达模式,发挥主要的负性免疫调节作用。除了在生理学上的意义外,LAIR1 的活性可能不适当涉及各种自身免疫或炎症性疾病,并与癌症病理生理学有关,包括血液系统肿瘤。作为抑制性受体,它可以导致免疫细胞反应失调,并在肿瘤微环境中发生免疫逃逸。此外,当肿瘤细胞表达 LAIR1 时,它可以调节肿瘤细胞的增殖或侵袭特性,根据肿瘤类型的不同,产生促肿瘤或抗肿瘤的作用。在这篇综述中,我们将重点介绍它在正常生理条件下以及在病理情况下(包括血液系统恶性肿瘤)的作用。我们还将讨论针对 LAIR1 的潜在治疗策略,用于治疗各种自身免疫性疾病和癌症。