Exposure to dim light at night prior to conception attenuates offspring innate immune responses

Functional circadian timekeeping is necessary for homeostatic control of the immune system and appropriate immune responsiveness. Disruption of natural light-dark cycles, through light at night (LAN), impairs innate and adaptive immune responses in nocturnal rodents. These altered immune responses are associated with disrupted endogenous gene transcriptional and endocrine cycles. However, few studies have addressed the multigenerational consequences of systemic circadian rhythm disruption. We hypothesized that parental exposure to dim LAN (dLAN) would alter innate immune and sickness responses to an endotoxin challenge in adult offspring gestated and reared in dark nights. Adult male and female Siberian hamsters were exposed to either dark nights (DARK) or dLAN (~5 lux) for 8 weeks, then paired, mated, and thereafter housed under dark nights. Maternal exposure to dLAN prior to conception impaired febrile responses and increased splenic il-1 production in response to LPS in male offspring. Paternal pre-conception dLAN dampened offspring tnf-α expression in the hypothalamus, reduced serum bactericidal capacity, and dark phase locomotor activity. These changes occurred despite offspring being conceived, gestated, and reared under standard dark night conditions. Overall, these data suggest that dLAN has intergenerational effects on innate immunity and sickness responses.

功能性昼夜节律计时对于免疫系统的稳态调控以及恰当的免疫应答至关重要。夜间光照（Light at Night, LAN）会破坏自然明暗周期，损害夜行性啮齿动物的先天与适应性免疫应答。这类异常的免疫应答与内源性基因转录及内分泌周期紊乱密切相关。然而，目前鲜有研究探讨全身性昼夜节律紊乱的跨代效应。本研究假设，亲代暴露于昏暗夜间光照（dim Light at Night, dLAN），会使在暗环境中受孕、妊娠并抚育的成年子代，在受到内毒素刺激时的先天免疫与疾病应答发生改变。将成年雌雄西伯利亚仓鼠分别置于正常暗环境（DARK）或昏暗夜间光照（~5勒克斯的dLAN）环境中暴露8周，随后进行配对交配，之后均饲养于正常暗环境中。受孕前母体暴露于dLAN，会导致雄性子代的发热应答受损，且在脂多糖（Lipopolysaccharide, LPS）刺激下脾脏白细胞介素1（interleukin-1, IL-1）的生成量升高。父代受孕前暴露于dLAN，则会抑制子代下丘脑的肿瘤坏死因子α（tumor necrosis factor-α, TNF-α）表达，降低血清杀菌能力以及暗周期运动活性。尽管子代均是在标准暗环境中受孕、妊娠并抚育的，上述变化仍会发生。综上，本研究数据表明，dLAN会对先天免疫与疾病应答产生跨代影响。