Autoimmune disorders are outcomes of impaired activity of the immune system regarding the maintenance of tolerance, which results in tissue damage secondary to an excess in the inflammatory response. Under normal conditions, the cells in the adaptive immune system are highly controlled to remain unresponsive against self-antigens (self-Ags) through various mechanisms and during different stages of maturation. CD69 (cluster of differentiation 69), a C–type lectin disulfide–linked homodimer, is expressed on different leukocytes, including newly-activated lymphocytes, certain subtypes of memory T-cells, infiltrating lymphocytes isolated from patients with chronic inflammatory disorders, and regulatory T-cells (Tregs). Cumulative evidence from in vitro and in vivo studies has revealed an immunoregulatory role for CD69. This marker has been reported to play a controversial role in chronic human inflammatory disorders. Many investigations have linked the absence of CD69 with a predisposition to inflammatory and/or autoimmune conditions, which indicates an immunoregulatory function for CD69 by mechanisms such as controlling the balance between differentiation of Th/Treg cells and enhancing the suppressive activity of Tregs. However, some reports from human studies have indicated that CD69 may exert a stimulatory effect on the inflammatory response. In this review, we first present a brief summary of the concept of ‘immune tolerance’ and, subsequently, review previous studies to uncover the details that underlie the immunoregulatory effects of CD69.

自身免疫性疾病是免疫系统在维持耐受性方面的活动受损的结果，这导致继发于炎症反应过度的组织损伤。在正常情况下，适应性免疫系统中的细胞受到高度控制，以通过各种机制和不同的成熟阶段对自身抗原（自身抗原）保持无反应。CD69（分化簇 69）是一种 C 型凝集素二硫化物连接的同源二聚体，在不同的白细胞上表达，包括新激活的淋巴细胞、某些亚型的记忆 T 细胞、从慢性炎症性疾病患者中分离出的浸润淋巴细胞和调节性T 细胞（Tregs）。来自体外和体内的累积证据研究揭示了 CD69 的免疫调节作用。据报道，该标志物在慢性人类炎症性疾病中发挥着有争议的作用。许多研究将 CD69 的缺失与炎症和/或自身免疫性疾病的易感性联系起来，这表明 CD69 通过控制 Th/Treg 细胞分化之间的平衡和增强 Tregs 抑制活性等机制发挥免疫调节功能。然而，一些来自人类研究的报告表明 CD69 可能对炎症反应产生刺激作用。在这篇综述中，我们首先简要总结了“免疫耐受”的概念，随后回顾了以前的研究，以揭示 CD69 免疫调节作用背后的细节。