Neurotrophic factor Neuritin modulates T cell electrical and metabolic state for the balance of tolerance and immunity.

Abstract

The adaptive T cell response is accompanied by continuous rewiring of the T cell's electric and metabolic state. Ion channels and nutrient transporters integrate bioelectric and biochemical signals from the environment, setting cellular electric and metabolic states. Divergent electric and metabolic states contribute to T cell immunity or tolerance. Here, we report in mice that neuritin (<i>Nrn1</i>) contributes to tolerance development by modulating regulatory and effector T cell function. <i>Nrn1</i> expression in regulatory T cells promotes its expansion and suppression function, while expression in the T effector cell dampens its inflammatory response. <i>Nrn1</i> deficiency in mice causes dysregulation of ion channel and nutrient transporter expression in Treg and effector T cells, resulting in divergent metabolic outcomes and impacting autoimmune disease progression and recovery. These findings identify a novel immune function of the neurotrophic factor <i>Nrn1</i> in regulating the T cell metabolic state in a cell context-dependent manner and modulating the outcome of an immune response.