Immune response efficiency is tuned by the biological clock

Dr. Nicolas Cermakian

A group of researchers led by Nicolas Cermakian (McGill University, Douglas Research Centre) and Nathalie Labrecque (Université de Montréal, Hôpital Maisonneuve-Rosemont Research Centre) has just identified the mechanisms that control the function of specific immune cells, CD8 T lymphocytes, according to the time of day. This study, published this week in the Proceedings of the National Academy of Sciences, will help to develop more efficient vaccination tools and should lead to new applications in immunotherapy against cancer.

An individual’s immune system is on continuous alert to detect invaders. These invaders are either different infectious microbes (viruses, bacteria, parasites) or the individual’s own cells that have become cancerous. The recognition of foreign elements by CD8 T lymphocytes leads to a variety of immune responses that will result in the elimination of the pathogens or cancerous cells.

Numerous aspects of our physiology present 24h (circadian) rhythms: sleep-wake cycles, feeding, hormones, body temperature, etc. These circadian rhythms allow organisms to be well-adapted to the cyclical variations in their environment (day-night cycles, seasons). Circadian rhythms are generated by biological clocks that are composed of “clock genes”, which influence most of organs and cells. This includes cells of our immune system, whose function varies throughout the day and night.

Previous work (including the Cermakian and Labrecque labs) had demonstrated that T cells responses to foreign elements varied in strength depending on the time of day. However, the role of the biological clock in this variation was unknown. In this new study, researchers used a vaccination model in mice to answer this question. Following the administration of the vaccine, CD8 T cells responded more or less strongly, depending on the time of day. Mice without a clock in their CD8 T cells lost this rhythm, highlighting the importance of this clock. Further, researchers demonstrated that numerous aspects of these cells make them ready to respond more strongly during daytime and to be less effective during nighttime. This new study shines a light on how the biological clock affects a variety of features of immune cells to make them more or less ready to fight microbes, or to respond to a vaccine.

 

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