Constant light exposure impairs immune tolerance development in mice

Background: An intrinsic daily physiological rhythm called circadian rhythm has been indicated to affect the immune system and its related diseases. Immune tolerance development is closely associated with the onset of immunological disorders. However, the effect of circadian rhythm in the mechanisms of immune tolerance development has not yet been fully understood. Objective: The purpose of this study was to investigate the effects of circadian rhythm disruption on the development of immune tolerance by the perturbation of light environment, using a mouse model of neonatally induced cutaneous tolerance. Methods: Mice were kept under constant light (LL) or light-dark (LD) conditions, and hapten was applied at 2 days after birth. Six weeks later, hapten was reapplied to abdominal skin, followed by hapten application to ear skin 5 days later. Results: The ear-swelling responses and cell infiltration into inflamed skin significantly increased in LL mice compared with those in LD mice. Interestingly, the percentage and the number of Foxp3(+)-regulatory T cells notably decreased in inflamed skin and draining lymph nodes of LL mice compared with that in LD mice. Loss-of-function mutation of a key circadian gene, Bmal1, also exacerbated the ear-swelling responses and cell infiltration into inflamed skin in mice. Conclusion: These results suggest that circadian rhythm may be implicated in immune tolerance development in allergic inflammation. (C) 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.