PING-MIN CHENKatsuyama, EriEriKatsuyamaSatyam, AbhigyanAbhigyanSatyamLi, HaoHaoLiRubio, JoseJoseRubioJung, SungwookSungwookJungAndrzejewski, SylviaSylviaAndrzejewskiBecherer, J DavidJ DavidBechererTsokos, Maria GMaria GTsokosAbdi, RezaRezaAbdiTsokos, George CGeorge CTsokos2023-02-092023-02-092022-06-172375-2548https://scholars.lib.ntu.edu.tw/handle/123456789/627793Infection 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.enN-ACETYLCYSTEINE; DISEASE-ACTIVITY; ERYTHEMATOSUS; DYSFUNCTION; ACTIVATION; COMPLEX; PRONE; AUTOIMMUNITY; LYMPHOCYTES; RAPAMYCINjournal article10.1126/sciadv.abo4271357045722-s2.0-85132883667WOS:000812533800034https://api.elsevier.com/content/abstract/scopus_id/85132883667