期刊
SCIENCE ADVANCES
卷 8, 期 24, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abo4271
关键词
-
资金
- NIH [R01AI148161]
CD38 up-regulation in CD8(+) T cells of SLE patients negatively affects T cell function by inhibiting mitochondrial fitness and mitophagy. Targeted administration of a CD38 inhibitor improves T cell function and viral clearance, suggesting CD38 as a potential therapeutic target to mitigate infection rates in people with SLE.
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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