Immune cells move to different parts of your body (from blood to organs and back) at different times of day.
Translated from: Circadian Expression of Migratory Factors Establishes Lineage-Specific Signatures that Guide the Homing of Leukocyte Subsets to Tissues
Main finding: This study, published in the journal Immunity, showed that there are different numbers of immune cells in blood (vs in organs) depending on the time of day that you look for them.
Why we care: The findings from this study could mean that drug treatments to turn down the immune system (immunosuppressants often given to treat autoimmune diseases such as arthritis, and to prevent rejection of transplant organs) or to boost the immune system (e.g. immunotherapy to treat cancer such as the treatment for which the 2018 Nobel prize in Physiology or Medicine was awarded), will be more effective if given at certain times of day. These findings also highlight the fact that research of immune cells needs to account for the potential effect that time of day could have. This could mean always doing your experiments at the same time of day, intentionally doing them at different times of day, or just recording what time of day your experiment has been done so that you can include this in your analysis.
How they worked it out: There are multiple types of immune cells, this study tested the total numbers of immune cells and 8 different types (termed subsets) of immune cells. When they took blood from laboratory mice at different times of day and night, they found that the total number of immune cells in the blood and the 8 different types of immune cells, was highest at midday (5 hours after the lights were turned on) and lowest at 8 pm (1 hour after the lights were turned off). The researchers also looked for where the immune cells had gone to make sure they had not just died off. They found that the immune cells had moved to different organs in the body with some types moving to the lungs and liver, and others moving to the spleen, bone marrow and lymph nodes. Immune cells did not go the skin and gut.
There are several steps involved when cells move from the bloodstream into the organs. The cells lining the blood vessels (endothelial cells) stick out proteins that the immune cells bind to (adhesion molecules), this slows the immune cells down. Infected and activated cells also help; they produce proteins that certain immune cells are attracted to (chemoattractants or chemokines) and thus move towards, this directs the immune cells to the target area. In this study, the researchers measured how many of these adhesion molecules and chemoattractants were being produced at different times of day. They found that at the times where there were fewer immune cells in the blood, there were more of these molecules present, this means that the immune cells were getting a signal to leave the blood from the blood vessels and organs.
Importantly, they also checked whether this day/night change happens in people. Here they found that only 4 types of immune cells had a day/night patterns and for 3 out of 4 of these, their pattern was opposite to mice in that they were lowest at 11am and highest at 9pm. This difference between people and mice make sense because mice are nocturnal (active at night) whereas people are diurnal (active during the day). Also, it is expected that they would see stronger effects in mice compared to people because unlike people, the mice are genetically identical (thanks to generations of inbreeding) and as laboratory mice they have always been in a very controlled environment with consistent 12hour day/night patterns and diet etc.
Original publication: He W. & friends published in Immunity, December 2018
10.1016/j.immuni.2018.10.007
