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

• DOI: 10.7554/elife.96812.2
• Publication Date: 2024-10-23T16:25:33Z
• Authors: Hong Yu; Hiroshi Nishio; Joseph Barbi; Marisa Mitchell-F...; Paolo DA Vignali; Ying Zheng; Andriana Lebid; Kwang-Yu Chang; Juan Fu; Makenzie Higgins; Ching-Tai Huang; Xuehong Zhang; Zhiguang Li; Lee Blosser; Ada Tam; Charles G Drake; Drew M Pardoll
• Keywords: cell fate; QH301-705.5; Science; autoimmunity; Q; R; Article; Treg; Immunology and Inflammation; effector T cell; Medicine; Biology (General); electric state; metabolism

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 that neuritin (Nrn1) contributes to tolerance development by modulating regulatory and effector T cell function. Nrn1 expression in regulatory T cells promotes its expansion and suppression function, while expression in the T effector cell dampens its inflammatory response. Nrn1 deficiency 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 Nrn1 in regulating the T cell metabolic state in a cell context-dependent manner and modulating the outcome of an immune response.