The pivotal role of CD69 in autoimmunity

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.