Therapeutic approaches, including neuronal gene delivery, recombinant GDF-15 administration and targeted chemogenetic activation of GFRAL-positive neurons induce β-adrenergic signaling and norepinephrine synthesis in the spleen, leading to decreased expression of integrins on T cells required for transmigration across the blood-brain barrier and confer protection against neuroinflammation in preclinical models of MS. The gene discussed is GFRAL; the disease is myeloid sarcoma.