The migration of dendritic cells from the skin into lymphatic vessels depends on the time of day. By understanding the cell migration systems underlying the immune reaction, scientists from the University of Geneva (UNIGE), in Switzerland, and the Ludwigs-Maximilians University (LMU), in Germany, have actually shown that the activation of the immune system is modulated according to the time of day. The migration of immune cells from the skin to the lymph nodes oscillates over a 24-hours duration. Unlike the innate immune system, which reacts right away but in a non-targeted way, the adaptive immune system constructs a long-lasting response specific to each transmittable agent. “For cell migration to take location properly, not just the dendritic cells however also the lymphatic vessel cells should respond to a circadian rhythm,” discusses Stephan Holtkamp, then a researcher at the Biomedical Center of the Ludwig-Maximilian University and very first author of this study.
To comprehend the function of circadian rhythms on immune activation, the scientists took a look at the migration of dendritic cells from the skin into the lymphatic system, among the pillars of the adaptive immune reaction. Found in many peripheral organs, including the skin, dendritic cells move through the lymphatic vessels to the lymph nodes, where antigens exist, in order to trigger an immune response versus an inbound pathogen.
Integrated clocks
The scientists first observed the migratory capability of dendritic cells in wild mice 4 times a day, then in mice without functional internal clocks. “For cell migration to take place correctly, not only the dendritic cells however likewise the lymphatic vessel cells must react to a circadian rhythm,” explains Stephan Holtkamp, then a researcher at the Biomedical Center of the Ludwig-Maximilian University and first author of this study.
The researchers then repeated their experiment on human skin cells drawn from clients at different times of the day. “We determined various particles, in specific chemokines, which are associated with the migratory process and whose expression is managed by circadian clocks,” states Christoph Scheiermann. “The exact same particles were found in human and mouse cells with an inverted rhythm corresponding to the life practices of the two species, nighttime for rodents, diurnal for humans. This validates that this rhythm is governed by natural activity according to the alternation of day and night.”
Stimulating the immune system at a favorable time
Additional information likewise suggest that if the immune system is stimulated at various times of the day, the same oscillations appear, with a peak in the morning. Why is the immune system governed by an oscillatory rhythm? The value of the circadian rhythm on the immune system is only just being to be revealed and might be of major significance both for preventive vaccination and for the administration of anti-tumor therapies or the management of autoimmune diseases.
Referral: “Circadian clocks assist dendritic cells into skin lymphatics” by Stephan J. Holtkamp, Louise M. Ince, Coline Barnoud, Madeleine T. Schmitt, Flore Sinturel, Violetta Pilorz, Robert Pick, Stéphane Jemelin, Michael Mühlstädt, Wolf-Henning Boehncke, Jasmin Weber, David Laubender, Julia Philippou-Massier, Chien-Sin Chen, Leonie Holtermann, Dietmar Vestweber, Markus Sperandio, Barbara U. Schraml, Cornelia Halin, Charna Dibner, Henrik Oster, Jörg Renkawitz and Christoph Scheiermann, 18 October 2021, Nature Immunology.DOI: 10.1038/ s41590-021-01040-x.
The migration of dendritic cells from the skin into lymphatic vessels depends on the time of day. Mouse dendritic cells (green) migrating into the lymphatic vessels (red).
Swiss and German scientists reveal that activation of the immune system oscillates throughout the day, with a peak prior to the start of the day.
By figuring out the cell migration systems underlying the immune action, scientists from the University of Geneva (UNIGE), in Switzerland, and the Ludwigs-Maximilians University (LMU), in Germany, have actually revealed that the activation of the immune system is modulated according to the time of day. The migration of immune cells from the skin to the lymph nodes oscillates over a 24-hours duration.
Unlike the inherent immune system, which reacts right away but in a non-targeted way, the adaptive immune system develops a long-term reaction specific to each contagious agent.” The adaptive immune system takes weeks to form a reaction specific to a given pathogen.