RT info:eu-repo/semantics/article
T1 Protein kinase C-η controls CTLA-4–mediated regulatory T cell function
A1 Kong, Kok-Fai
A1 Fu, Guo
A1 Zhang, Yaoyang
A1 Yokosuka, Tadashi
A1 Casas, Javier
A1 Canonigo-Balancio, Ann J
A1 Becart, Stephane
A1 Kim, Gisen
A1 Yates, John R
A1 Kronenberg, Mitchell
A1 Saito, Takashi
A1 Gascoigne, Nicholas R J
A1 Altman, Amnon
AB Regulatory T (Treg) cells, which maintain immune homeostasis and self-tolerance, form an immunological synapse (IS) with antigen-presenting cells (APCs). However, signaling events at the Treg cell IS remain unknown. Here we show that the kinase PKC-η associated with CTLA-4 and was recruited to the Treg cell IS. PKC-η-deficient Treg cells displayed defective suppressive activity, including suppression of tumor immunity but not of autoimmune colitis. Phosphoproteomic and biochemical analysis revealed an association between CTLA-4-PKC-η and the GIT2-αPIX-PAK complex, an IS-localized focal adhesion complex. Defective activation of this complex in PKC-η-deficient Treg cells was associated with reduced depletion of CD86 from APCs by Treg cells. These results reveal a CTLA-4-PKC-η signaling axis required for contact-dependent suppression and implicate this pathway as a potential cancer immunotherapy target.
SN 1529-2908
YR 2014
FD 2014
LK https://uvadoc.uva.es/handle/10324/64301
UL https://uvadoc.uva.es/handle/10324/64301
LA eng
NO Nature Immunology 15:465–472. https://doi.org/10.1038/ni.2866
NO Producción Científica
DS UVaDOC
RD 21-jun-2024