The immunological clock: the role of cryptochrome in regulatory T cell function (IRM15P.602)

Abstract

Abstract Circadian rhythms are defined as 24 hour oscillations in physiological and behavioral processes. Clinical data suggests circadian involvement in the predisposition and progression of immune-related morbidities such as cancer and autoimmune disease. Recent studies have demonstrated the direct role of core molecular clock components in maintaining the immune system. A subset of CD4+ T cells known as regulatory T cells (Treg) are critical for preserving balance in the immune system and have been shown to be able to prevent a broad range of autoimmune disease. By studying the role of core circadian genes in Treg cells the connection between the circadian clock and autoimmune disease may be further elucidated. We have identified a core circadian clock gene, cryptochrome (Cry), to have a role in Treg cell function both in vitro and in vivo. The deficiency of Cry in Treg cells results in a breakdown in immune tolerance, which results in severe pathological autoimmunity in mice. This is characterized by immune cell infiltration into peripheral tissues as well as increased numbers of cytokine producing CD4 and CD8 T cells. It was also seen that ectopic expression of Cry in Treg cells results in increased suppression of T cell proliferation in vitro. Thus, we have demonstrated a direct role of Cry expression in the function of Treg cells.