Signaling function of PRC2 is essential for TCR-driven T cell responses.
J Exp Med
; 215(4): 1101-1113, 2018 04 02.
Article
en En
| MEDLINE
| ID: mdl-29523590
ABSTRACT
Differentiation and activation of T cells require the activity of numerous histone lysine methyltransferases (HMT) that control the transcriptional T cell output. One of the most potent regulators of T cell differentiation is the HMT Ezh2. Ezh2 is a key enzymatic component of polycomb repressive complex 2 (PRC2), which silences gene expression by histone H3 di/tri-methylation at lysine 27. Surprisingly, in many cell types, including T cells, Ezh2 is localized in both the nucleus and the cytosol. Here we show the presence of a nuclear-like PRC2 complex in T cell cytosol and demonstrate a role of cytosolic PRC2 in T cell antigen receptor (TCR)-mediated signaling. We show that short-term suppression of PRC2 precludes TCR-driven T cell activation in vitro. We also demonstrate that pharmacological inhibition of PRC2 in vivo greatly attenuates the severe T cell-driven autoimmunity caused by regulatory T cell depletion. Our data reveal cytoplasmic PRC2 is one of the most potent regulators of T cell activation and point toward the therapeutic potential of PRC2 inhibitors for the treatment of T cell-driven autoimmune diseases.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Antígenos de Linfocitos T
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Linfocitos T
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Transducción de Señal
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Complejo Represivo Polycomb 2
Límite:
Animals
Idioma:
En
Año:
2018
Tipo del documento:
Article