Number and function of circulating human antigen presenting cells regulated by sleep

Abstract

Study Objectives: There is evidence that sleep facilitates the adaptive immune response to infectious agents and, thereby, supports immunologic memory. The effect might be attained by sleep-induced changes in the number and function of dendritic cells (DCs), which play a key role in the initiation of the immune response. This study aimed to dissociate effects of sleep and circadian rhythm on circulating numbers of DC precursors, ie, CD14+CD16- and CD14dimCD16+ monocytes, myeloid dendritic cell precursors (pre-mDC), and plasmacytoid dendritic cells (PDC) and on 2 key cytokines produced by these cells, ie, interleukin (IL)-12 and interferon (IFN)-α. Design: In a within-subject cross-over design, human subjects were examined on 2 occasions, ie, during a normal sleep-wake cycle and during 24 hours of wakefulness. Blood was sampled every 1.5 hours during nighttime and every 3 hours during daytime. Setting: Experiments took place under controlled laboratory conditions. Participants: Twenty-seven healthy men aged between 18 and 30 years. Measurements and Results: Compared with wakefulness, sleep was associated with a striking increase in the number of pre-mDC producing IL-12, which is a main inducer of Th1 responses. In addition, sleep slightly decreased PDC and also T cell counts but did not affect IFN-α production by PDC. Sleep, however, substantially decreased numbers of CD14dimCD16 + monocytes, probably reflecting increased margination of the cells upon a sleep-related drop in catecholamine release. Conclusions: Our data identify pre-mDC producing IL-12 as a basic target of sleep that is most closely related to mature APC function and whereby sleep can effectively enhance adaptive immune responses.