Circadian control of leukocyte numbers in the circulation

Hergenhan, Sophia Martina (2020): Circadian control of leukocyte numbers in the circulation. Dissertation, LMU München: Medizinische Fakultät

Abstract

Circadian rhythms play an important role in determining the strength of the immune response. Key entrainment factors for these oscillations are light, behaviour and food intake. It has previously been shown that leukocyte mobilization from the bone marrow fluctuates over the course of the day. In addition, leukocyte homing to organs contributes to an oscillatory cell count in the circulation. However, it is currently unclear which factors determine oscillations in blood cellularity. Leukocyte numbers were investigated after altering the main entrainment factors and timed feeding was able to phase-shift rhythms in white blood cell numbers in blood, while light was only able to shape these rhythms. Additionally, germ-free animals exhibited lower leukocyte counts at specific times and reduced oscillations in overall cellularity. Serum transfer experiments revealed increased leukocyte numbers in the circulation at specific times. These increases could be prevented by genetic ablation of toll-like receptor adaptor molecule MyD88 or pharmacological targeting of inflammatory cytokines. On a molecular level, time-restricted feeding (TRF) phase-shifted clock gene expression in peripheral organs that receive input from the gut and leukocytes from germ-free animals exhibited altered expression of migratory factors. It is known that TRF induces circadian rhythms in microbiota composition, orchestrated by the central clock. Additionally, commensal bacteria influence the immune system by priming innate immune cells for potential infections. Taken together, these data propose a daily steady-state inflammation as part of normal host physiology, leading to rhythmic leukocyte numbers in blood. This physiological immune priming is mediated by rhythms in commensal bacteria, controlled by timed food uptake.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Circadian, Immunology
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 25. März 2020
• 1. Bericht­erstatter:in: Scheiermann, Christoph