Regulation of CD4⁺ and CD8⁺ Effector Responses by Sprouty-1

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Nov 21

PMID 23166773

Citations 11

Authors

Sam Collins

Adam Waickman

Albert Basson

Abraham Kupfer

Jonathan D Licht

Maureen R Horton

Jonathan D Powell

Affiliations

Soon will be listed here.

Abstract

TCR-induced NF-AT activation leads to the expression of both activating and inhibitory proteins. Previously, we had identified Egr-2 and Egr-3 as NF-AT-induced transcription factors which promote the inhibition of T cell activation. In this report we identify Sprouty1 as a downstream target of Egr-3. CD4⁺ T cells lacking Spry1 demonstrate enhanced proliferation and cytokine production. Likewise, Spry1(Flox/Flox) Lck Cre CD8⁺ T cells display increased cytolytic activity. Mechanistically, Spry1 acts at the level of PLC-γ promoting the inhibition of both Ca⁺⁺ induced NF-AT activation and MAP-kinase induced AP-1 activation while sparing NF-κB signaling. In vivo, mice in which Spry1 is selectively deleted in T cells demonstrate enhanced responses to a tumor vaccine and subsequently reject tumors more robustly than Wt mice. These findings suggest that targeting Spry1 might prove to be a novel means of enhancing tumor immunotherapy.

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