Abstract |
Infection is one of the major causes of mortality in patients with systemic lupus erythematosus (SLE). We previously found that CD38, an ectoenzyme that regulates the production of NAD+, is up-regulated in CD8+ T cells of SLE patients and correlates with the risk of infection. Here, we report that CD38 reduces CD8+ T cell function by negatively affecting mitochondrial fitness through the inhibition of multiple steps of mitophagy, a process that is critical for mitochondria quality control. Using a murine lupus model, we found that administration of a CD38 inhibitor in a CD8+ T cell-targeted manner reinvigorated their effector function, reversed the defects in autophagy and mitochondria, and improved viral clearance. We conclude that CD38 represents a target to mitigate infection rates in people with SLE.
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Authors | Ping-Min Chen, Eri Katsuyama, Abhigyan Satyam, Hao Li, Jose Rubio, Sungwook Jung, Sylvia Andrzejewski, J David Becherer, Maria G Tsokos, Reza Abdi, George C Tsokos |
Journal | Science advances
(Sci Adv)
Vol. 8
Issue 24
Pg. eabo4271
(06 17 2022)
ISSN: 2375-2548 [Electronic] United States |
PMID | 35704572
(Publication Type: Journal Article)
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Topics |
- Animals
- CD8-Positive T-Lymphocytes
(metabolism)
- Humans
- Lupus Erythematosus, Systemic
(metabolism)
- Mice
- Mitochondria
- Mitophagy
- Virus Diseases
(metabolism)
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