The Neuroimmune Connectome: Understanding how the Peripheral Nervous System shapes Immunity

Nerves are active regulators of immunity. Here, we review the current understanding of neuroimmune communication, focusing on how peripheral neurons instruct immune cell differentiation and function. We discuss mechanisms by which neurotransmitters, neuropeptides, and cytokines mediate reciprocal signaling between nerves and immune cells across infection, allergy, autoimmunity, and cancer. We introduce the concept of nerves as "state-setters" of immunity and summarize emerging therapeutic strategies that target neuroimmune pathways. Finally, we highlight current methodological challenges and outline priorities for mapping the peripheral neuroimmune connectome to accelerate clinical translation.