RT Journal Article
T1 The CD38/NAD/SIRTUIN1/EZH2 Axis Mitigates Cytotoxic CD8 T Cell Function and Identifies Patients with SLE Prone to Infections
A1 Katsuyama, Eri
A1 Tsokos, George C
A1 Marín Marín, Ana Victoria
AB Patients with systemic lupus erythematosus (SLE) suffer frequent infections that account for significant morbidity and mortality. T cell cytotoxic responses are decreased in patients with SLE, yet the responsible molecular events are largely unknown. We find an expanded CD8CD38high T cell subset in a subgroup of patients with increased rates of infections. CD8CD38high T cells from healthy subjects and patients with SLE display decreased cytotoxic capacity, degranulation, and expression of granzymes A and B and perforin. The key cytotoxicity-related transcription factors T-bet, RUNX3, and EOMES are decreased in CD8CD38high T cells. CD38 leads to increased acetylated EZH2 through inhibition of the deacetylase Sirtuin1. Acetylated EZH2 represses RUNX3 expression, whereas inhibition of EZH2 restores CD8 T cell cytotoxic responses. We propose that high levels of CD38 lead to decreased CD8 T cell-mediated cytotoxicity and increased propensity to infections in patients with SLE, a process that can be reversed pharmacologically.
PB Cell Press
YR 2020
FD 2020-01-07
LK https://hdl.handle.net/20.500.14352/113930
UL https://hdl.handle.net/20.500.14352/113930
LA eng
NO Katsuyama E, Suarez-Fueyo A, Bradley SJ, Mizui M, Marin AV, Mulki L, Krishfield S, Malavasi F, Yoon J, Sui SJH, Kyttaris VC, Tsokos GC. The CD38/NAD/SIRTUIN1/EZH2 Axis Mitigates Cytotoxic CD8 T Cell Function and Identifies Patients with SLE Prone to Infections. Cell Rep. 2020 Jan 7;30(1):112-123.e4. doi: 10.1016/j.celrep.2019.12.014. PMID: 31914379; PMCID: PMC7577012.
DS Docta Complutense
RD 12 abr 2025