CRC 654, Project C08: Sleep-circadian oscillations in cytokine regulation

Project: DFG ProjectsDFG Joint Research: Collaborative Research Center/ Transregios

Project Details


Project C 08 of DFG CRC 654 "Plasticity and Sleep"

Results from the current funding period show a close functional link between sleep, circadian clock and CD4+ T cell function. Thus, we could show that the expression of pro- and anti-inflammatory cytokines by CD4+ cells is regulated in a diurnal as well as sleep-dependent manner. Experiments with murine thymocytes as well as thymic and lymph node slice cultures also show an endogenously regulated rhythmic expression of the circadian clock protein PER2, synchronous to the also rhythmic expression of CD40L and IFN-. In the upcoming funding period, we aim to elucidate the mechanisms of this interplay between (CD4+) T cell clock, sleep and immune functions. Our data to date suggest two distinct scenarios: (i) Nocturnal sleep represents a permissive state that enables circadian rhythmic regulation of immune function. (ii) Sleep itself-or sleep deprivation-functions as a timer for local immune cell clocks, synchronizing T cell activity and activity rhythms. To test these hypotheses, we generated mice with genetically induced complete loss of clock function as well as animals with a defect in clock machinery specifically in T cells. Using these model animals, we aim to compare the lymphocyte profile (number, function in vivo and in vitro) of wild-type mice with that of circadian arhythmic Per1/2 double mutants and mutants with T cell-specific deletion of the circadian clock machinery (Lck-Cre x Bmal1-flox) at different times of day and sleep conditions. Cells will be treated in vitro in culture with clock- and sleep-dependent factors (glucocorticoids, norepinephrine, growth hormone or inhibitors of the corresponding receptors) and tested for their activity (expression of IL-2, IL-4, IFN-γ, IL-17) after stimulation with PMA/ionomycin. The derived principles will then be validated in human cells under different sleep conditions. To investigate the influence of the interaction of sleep and circadian clock on the immune response also in vivo, the above mentioned mouse strains will be infected with either Leishmania (as a model for a chronic infection) or immunized with myelin oligodendrocyte glycoprotein (MOG; as a model for a chronic autoimmune inflammation) at different circadian times and under different sleep conditions and subsequently the disease course as well as T cell and T cell clock functions will be analyzed.
Effective start/end date01.01.0931.12.17

UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

DFG Research Classification Scheme

  • 205-17 Endocrinology, Diabetology, Metabolism
  • 204-05 Immunology
  • CRC 654: Plasticity and Sleep

    Born, J.


    Project: DFG ProjectsDFG Joint Research: Collaborative Research Center/ Transregios