Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure. Physiol Genomics 48: 526 -536, 2016. First published May 27, 2016 doi:10.1152/physiolgenomics.00039.2016 is a prevalent condition with complex etiology and pathophysiology. Evidence exists of significant communication between the nervous system and the immune system (IS), and there appears to be a direct role for inflammatory bone marrow (BM) cells in the pathophysiology of hypertension. However, the molecular and neural mechanisms underlying this interaction have not been characterized. Here, we transplanted whole BM cells from the beta 1 and 2 adrenergic receptor (AdrB1 tm1Bkk AdrB2 tm1Bkk /J) knockout (KO) mice into near lethally irradiated C57BL/6J mice to generate a BM AdrB1.B2 KO chimera. This allowed us to evaluate the role of the BM beta 1 and beta 2 adrenergic receptors in mediating BM IS homeostasis and regulating blood pressure (BP) in an otherwise intact physiological setting. Fluorescence-activated cell sorting demonstrated that a decrease in systolic and mean BP in the AdrB1.B2 KO chimera is associated with a decrease in circulating inflammatory T cells, macrophage/monocytes, and neutrophils. Transcriptomics in the BM identified 7,419 differentially expressed transcripts between the C57 and AdrB1.B2 KO chimera. Pathway analysis revealed differentially expressed transcripts related to several cell processes in the BM of C57 compared with AdrB1.B2 KO chimera, including processes related to immunity (e.g., T-cell activation, T-cell recruitment, cytokine production, leukocyte migration and function), the cardiovascular system (e.g., blood vessel development, peripheral nerve blood flow), and the brain (e.g., central nervous system development, neurite development) among others. This study generates new insight into the molecular events that underlie the interaction between the sympathetic drive and IS in modulation of BP. adrenergic receptors; immune system; bone marrow; chimera; sympathetic drive DYNAMIC INTERPLAY BETWEEN the immune system (IS) and the central nervous system (CNS) exists for physiological homeostasis. The autonomic arm of the CNS, specifically the sympathetic nervous system (SNS), contributes to the diurnal function of the IS by modulating the development and release of bone marrow (BM) hematopoietic cells into circulation via the activation of beta adrenergic receptors expressed by these cells (17,18,25). Activation of the BM beta 1 and 2 adrenergic receptors, in particular, has been shown to modulate the levels of different immune cells in circulation, with inflammatory cells predominantly released during the highest activity period [i.e., night time in rodents and day time in humans (5, 9, 17, 18, 25)], an evolutionary mechanism developed to prime the system for warding off infection, should the need arise. On the other hand, the reciprocal action of an activated IS on the CNS has also been suggested, with significant evid...