The nervous system and the immune system are the body’s two large sensory units, which together constantly monitor and regulate body homeostasis. The coordination of both systems needs to be tightly regulated and is based on bidirectional crosstalk, which requires a steady exchange of information. Neurons communicate via secretion of neuropeptides and neurotransmitters and hematopoietic cells express receptors for some of these factors providing a molecular basis for neuronal regulation of immune responses. Evidence from both mice and humans suggests that regulation of immune responses via the sympathetic nervous system and β2-adrenergic receptors (Adrb2) on myeloid cells is involved in the pathogenesis of chronic inflammatory diseases. However, how sympathetic immune regulation is mediated on a cellular and molecular level concerning the neuronal system and myeloid cells remains poorly understood. We propose to systematically investigate immune regulation by Adrb2 in the central nervous system and the intestine using conditional deletion of Adrb2 in neutrophils, macrophages, and dendritic cells. We scrutinize the neuronal pathway by modulating the activation threshold of sympathetic neurons by overexpression of designer drug receptors or by acute or chronic constraint stress induction. These models will be combined with nextgeneration sequencing approaches of myeloid cells and nuclei from neurons to dissect the molecular pathways triggered in these cell types that regulate chronic inflammation.