The CD38/NAD/SIRTUIN1/EZH2 Axis Mitigates Cytotoxic CD8 T Cell Function and Identifies Patients with SLE Prone to Infections
Eri Katsuyama, Abel Suárez‐Fueyo, Sean J. Bradley, Masayuki Mizui, Ana V. Marín, Lama Mulki, Suzanne Krishfield, Fabio Malavasi, Joon Yoon, Shannan J. Ho Sui, Vasileios C. Kyttaris, George C. Tsokos
Abstract
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.
Topics & Concepts
CD38Cytotoxic T cellNAD+ kinaseCD8ImmunologyChemistryT cellCytotoxicityBiologyCancer researchImmune systemCell biologyBiochemistryIn vitroStem cellEnzymeCD34Calcium signaling and nucleotide metabolismCytomegalovirus and herpesvirus researchAdenosine and Purinergic Signaling