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Control of circadian lymphocyte migration in lymphoid and non-lymphoid tissues by the sympathetic nervous system

Subject Area Immunology
Term from 2012 to 2019
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 224876142
 
Final Report Year 2019

Final Report Abstract

The recruitment of hematopoietic cells plays a crucial role in the immune response. In this proposal we have investigated whether circadian and neural influences regulate the migration of leukocytes to tissues. We could demonstrate that migratory oscillations of leukocytes exist for myeloid cells and lymphocytes into lymphoid and non-lymphoid organs. We could further show that also the egress from lymph nodes is dictated by the time of day. We have in this proposal demonstrated that even weeks after antigen exposure the adaptive immune response is governed by the specific time of day when the initial stimulus was applied. Mechanistically, we showed that deficiency in key clock genes in different leukocyte lineages ablates rhythmicity. Our data enforce the emerging paradigm that a properly tuned adaptive immune response is critical in immunity. Circadian, ~24 hour rhythms are emerging as critical regulators of immune cell function, which impacts innate and adaptive inflammatory diseases. Inducing or inhibiting adaptive immunity at the proper times provides an option for therapy that would maximize the clinical impact of drugs and vaccinations and minimize side effects.

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