Imperial College London
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Prof Liz Lightstone

Faculty of Medicine, Department of Immunology and Inflammation

Proconsul and Professor of Renal Medicine
 
 
 
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Contact

 

+44 (0)20 3313 3152l.lightstone Website CV

 
 
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Assistant

 

Miss Anjli Jagpal +44 (0)20 3313 3152

 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Botto:2021:10.1038/s41467-021-22312-y,
author = {Botto, M and Buang, N and Tapeng, L and Gray, V and Sardini, A and Whilding, C and Lightstone, L and Cairns, T and Pickering, M and Behmoaras, J and Ling, GS},
doi = {10.1038/s41467-021-22312-y},
journal = {Nature Communications},
pages = {1--15},
title = {Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus},
url = {http://dx.doi.org/10.1038/s41467-021-22312-y},
volume = {12},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The majority of patients with systemic lupus erythematosus (SLE) have high expression of type I IFN-stimulated genes. Mitochondrial abnormalities have also been reported, but the contribution of type I IFN exposure to these changes is unknown. Here, we show downregulation of mitochondria-derived genes and mitochondria-associated metabolic pathways in IFN-High patients from transcriptomic analysis of CD4+ and CD8+ T cells. CD8+ T cells from these patients have enlarged mitochondria and lower spare respiratory capacity associated with increased cell death upon rechallenge with TCR stimulation. These mitochondrial abnormalities can be phenocopied by exposing CD8+ T cells from healthy volunteers to type I IFN and TCR stimulation. Mechanistically these ‘SLE-like’ conditions increase CD8+ T cell NAD+ consumption resulting in impaired mitochondrial respiration and reduced cell viability, both of which can be rectified by NAD+ supplementation. Our data suggest that type I IFN exposure contributes to SLE pathogenesis by promoting CD8+ T cell death via metabolic rewiring.
AU  - Botto,M
AU  - Buang,N
AU  - Tapeng,L
AU  - Gray,V
AU  - Sardini,A
AU  - Whilding,C
AU  - Lightstone,L
AU  - Cairns,T
AU  - Pickering,M
AU  - Behmoaras,J
AU  - Ling,GS
DO  - 10.1038/s41467-021-22312-y
EP  - 15
PY  - 2021///
SN  - 2041-1723
SP  - 1
TI  - Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-021-22312-y
UR  - https://www.nature.com/articles/s41467-021-22312-y
UR  - http://hdl.handle.net/10044/1/88506
VL  - 12
ER  -
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