Neurotrophic factor Neuritin modulates T cell electrical and metabolic state for the balance of tolerance and immunity
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 ( 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 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 Nrn1 in regulating the T cell metabolic state in a cell context-dependent manner and modulating the outcome of an immune response.
Authors
- Marisa Mitchell-Flack (ORCID: https://orcid.org/0000-0003-3192-0865)
- Andriana Lebid (ORCID: https://orcid.org/0000-0002-8207-0605)
- Paolo Vignali (ORCID: https://orcid.org/0000-0002-0214-8629)
- Charles G. Drake (ORCID: https://orcid.org/0000-0001-9610-3677)
- Hiroshi Nishio (ORCID: https://orcid.org/0000-0002-4938-416X)
- Juan Fu
- Ching‐Tai Huang (ORCID: https://orcid.org/0000-0001-8624-4513)
- Drew M. Pardoll (ORCID: https://orcid.org/0000-0001-6215-1013)
- Ada Tam (ORCID: https://orcid.org/0000-0001-6828-5290)
- Makenzie Higgins
- Lee Blosser
- Joseph Barbi (ORCID: https://orcid.org/0000-0002-5632-0885)
- Zhiguang Li (ORCID: https://orcid.org/0000-0003-2474-3485)
- Xuehong Zhang (ORCID: https://orcid.org/0000-0001-8040-4141)
- Kwang‐Yu Chang (ORCID: https://orcid.org/0000-0002-5240-2760)
- Hong Yu (ORCID: https://orcid.org/0000-0002-8778-9870)
- Ying Zheng (ORCID: https://orcid.org/0000-0002-5264-6431)
Institutions
- Bloomberg (United States) (US)
- Johns Hopkins University (US)
- Dalian Medical University (CN)
- Sidney Kimmel Comprehensive Cancer Center (US)
Publication Details
- Journal
- eLife
- Published
- 2024-11-20
- DOI
- https://doi.org/10.7554/elife.96812.3
- Primary Topic
- Ion channel regulation and function
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Defense
- National Institute of General Medical Sciences