Protein Kinase C-η Controls CTLA-4-mediated Regulatory T Cell Function

Overview

Journal Nat Immunol

Date 2014 Apr 8

PMID 24705298

Citations 87

Authors

Kok-Fai Kong

Guo Fu

Yaoyang Zhang

Tadashi Yokosuka

Javier Casas

Ann J Canonigo-Balancio

Stephane Becart

Gisen Kim

John R Yates 3rd

Mitchell Kronenberg

Takashi Saito

Nicholas R J Gascoigne

Amnon Altman

Affiliations

Soon will be listed here.

Abstract

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.

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