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- Publisher Website: 10.1038/s41467-021-22312-y
- Scopus: eid_2-s2.0-85103744544
- PMID: 33790300
- WOS: WOS:000636879000001
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Article: Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus
Title | Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus |
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Authors | |
Issue Date | 2021 |
Publisher | Nature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html |
Citation | Nature Communications, 2021, v. 12 n. 1, p. article no. 1980 How to Cite? |
Abstract | 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. |
Persistent Identifier | http://hdl.handle.net/10722/299350 |
ISSN | 2023 Impact Factor: 14.7 2023 SCImago Journal Rankings: 4.887 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Buang, N | - |
dc.contributor.author | Tapeng, L | - |
dc.contributor.author | Gray, V | - |
dc.contributor.author | Sardini, A | - |
dc.contributor.author | Whilding, C | - |
dc.contributor.author | Lightstone, L | - |
dc.contributor.author | Cairns, TD | - |
dc.contributor.author | Pickering, MC | - |
dc.contributor.author | Behmoaras, J | - |
dc.contributor.author | Ling, GS | - |
dc.contributor.author | Botto, M | - |
dc.date.accessioned | 2021-05-10T07:00:32Z | - |
dc.date.available | 2021-05-10T07:00:32Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Nature Communications, 2021, v. 12 n. 1, p. article no. 1980 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/10722/299350 | - |
dc.description.abstract | 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. | - |
dc.language | eng | - |
dc.publisher | Nature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html | - |
dc.relation.ispartof | Nature Communications | - |
dc.rights | Nature Communications. Copyright © Nature Research: Fully open access journals. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus | - |
dc.type | Article | - |
dc.identifier.email | Ling, GS: gsling@hku.hk | - |
dc.identifier.authority | Ling, GS=rp02629 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1038/s41467-021-22312-y | - |
dc.identifier.pmid | 33790300 | - |
dc.identifier.pmcid | PMC8012390 | - |
dc.identifier.scopus | eid_2-s2.0-85103744544 | - |
dc.identifier.hkuros | 322421 | - |
dc.identifier.volume | 12 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | article no. 1980 | - |
dc.identifier.epage | article no. 1980 | - |
dc.identifier.isi | WOS:000636879000001 | - |
dc.publisher.place | United Kingdom | - |