AgRP neurons regulate hematopoiesis and Treg generation through beta 3 adrenergic receptor-expressing stromal cells

Maturation of hematopoietic stem and progenitor cells (HSPC) in bone marrow (BM) and of T-lymphocytes in thymus occurs within stromal areas innervated by adrenergic fibers of the sympathetic nervous system (SNS). Here we have discovered that in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), SNS signaling to specific stromal cells expressing beta 3 adrenergic receptors (B3AR) promote differentiation and mobilization of hematopoietic precursors in BM and generation of regulatory T-lymphocytes (Treg) in the thymus. We demonstrate that the functionality of B3AR on BM and thymic stromal cells is under control of hypothalamic neurons expressing Agouti-Related Protein (AgRP), which are activated in EAE. The finding that AgRP neuropeptide is increased in the serum of people with MS, supports that AgRP neurons might be activated also in MS. Overall design: Lineage-/Sca1+/cKit+ cells isolated from the bone marrow of 3 naive C57BL/6 mice; 3 C57BL/6 mice 3 days after immunization for EAE; 3 C57BL/6 mice immunized for EAE and treated for 3 days with SR59230A, an antagonist of beta 3 adrenergic receptors.