Emmy Noether Junior Research Group - Control of circadian lymphocyte migration in lymphoid and non-lymphoid tissues by the sympathetic nervous system
- Project Leader: Dr. Christoph Scheiermann
- Affiliation: Walter-Brendel-Centre of Experimental Medicine
- Funding: 2012 to 2019
The recruitment of hematopoietic cells plays a crucial role in the immune response. In this project we will investigate whether neural influences regulate the migration of lymphocytes in tissues. Preliminary data indicate that centrally-initiated systemic programs affect locally the infiltration of myeloid cells into tissues via adrenergic nerves of the sympathetic nervous system (SNS). This leads to a circadian oscillation in the recruitment of myeloid cells from the blood to the bone marrow and peripheral organs, exhibiting a peak at times of high physiological activity, i.e. at night in the mouse. We will base our studies on these preliminary data and investigate whether migratory oscillations also exist in the emigration of lymphocytes from the blood and which populations are affected in lymphoid and non-lymphoid organs. In addition, we will investigate in mechanistic detail, which promigratory factors control these rhythms and whether they can be altered by surgical, pharmacological or genetic interventions. To test the relevance of these oscillations we will investigate acute and chronic inflammatory reactions to assess whether the daily cycle influences the strength of the immune response. The anticipated results of this proposal will therefore provide novel mechanistic insight into the systemic regulation of lymphocyte trafficking by sympathetic nerves with the potential for time-based, i.e. chronotherapeutic, interventions in inflammatory diseases.