Increased homing of immune cells by orexigenic catecholaminergic neurons alleviates autoimmune disorder

Whole-body energy status significantly impacts the immune system. Both feeding behavior and energy metabolism are controlled by the central nerve system, but it is unknown whether the brain can regulate the immune system in response to fluctuations of the energy status. Here, we show that catecholaminergic (CA) neurons in the nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM) were activated by fasting, and demonstrate that chemogenetic activation of these hindbrain CA neurons both increased food intake and drove homing of CD45+ cells, T cells, and B cells from blood to bone marrow, which was mediated by enhanced HPA axis and upregulation of the chemokine receptor CXCR4. This activation of CA neurons also prevented immune cell infiltration to the brain in the experimental autoimmune encephalomyelitis (EAE) mouse model, and ameliorated the disease outcome. Our study demonstrates the neuronal control of immune function in response to host energy scarcity and sheds light on communications between the nervous and immune systems.