regulation of cd4+ and cd8+ effector responses by sprouty-1调节cd4 +和cd8 + sprouty-1效应反应.pdfVIP

Regulation of CD4+ and CD8+ Effector Responses by Sprouty-1 1 2 4 3 5 Sam Collins , Adam Waickman , Albert Basson , Abraham Kupfer , Jonathan D. Licht , 1 2 Maureen R. Horton , Jonathan D. Powell * 1 Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 2 The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 3 Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 4 Department of Craniofacial Development and Stem Cell Biology, Kings College, London, United Kingdom, 5 Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America 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, Spry1Flox/Flox Lck Cre CD8+ T cells display increased cytolytic activity. Mechanistically, Spry1 acts at the level of PLC-c promoting the inhibition of both Ca++ induced NF-AT activation and MAP-kinase induced AP-1 activation while sparing NF-kB signaling. In vivo, mice in which Spry1 is se