| Autor: |
Eri Katsuyama, Abel Suarez-Fueyo, Sean J. Bradley, Masayuki Mizui, Ana V. Marin, Lama Mulki, Suzanne Krishfield, Fabio Malavasi, Joon Yoon, Shannan J. Ho Sui, Vasileios C. Kyttaris, George C. Tsokos |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 30, Iss 1, Pp 112-123.e4 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.12.014 |
| Popis: |
Summary: 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. : Katsuyama et al. find that an expanded CD8CD38high T cell population in SLE patients is linked to infections. CD8CD38high T cells display decreased cytotoxic capacity by suppressing the expression of related molecules through an NAD+/Sirtuin1/EZH2 pathway. EZH2 inhibitors increase cytotoxicity offering a means to mitigate infection rates in SLE. Keywords: systemic lupus erythematosus, patients, CD8 T cell, CD38, cytotoxicity, infection, nicotinamide adenine dinucleotide, Sirtuin1, EZH2 |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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