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The receptor for advanced glycation endproducts (RAGE) modulates T cell signaling
Author(s) -
James C. Reed,
Paula Preston-Hurlburt,
William M. Philbrick,
Gabriel Betancur,
Maria Korah,
Carrie L. Lucas,
Kevan C. Herold
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0236921
Subject(s) - jurkat cells , rage (emotion) , signal transduction , zap70 , microbiology and biotechnology , t cell , cd28 , mapk/erk pathway , cancer research , biology , chemistry , immunology , il 2 receptor , immune system , neuroscience
The receptor for advanced glycation endproducts (RAGE) is expressed in T cells after activation with antigen and is constitutively expressed in T cells from patients at-risk for and with type 1 diabetes mellitus (T1D). RAGE expression was associated with an activated T cell phenotype, leading us to examine whether RAGE is involved in T cell signaling. In primary CD4+ and CD8+ T cells from patients with T1D or healthy control subjects, RAGE- cells showed reduced phosphorylation of Erk. To study T cell receptor signaling in RAGE+ or–T cells, we compared signaling in RAGE+/+ Jurkat cells, Jurkat cells with RAGE eliminated by CRISPR/Cas9, or silenced with siRNA. In RAGE KO Jurkat cells, there was reduced phosphorylation of Zap70, Erk and MEK, but not Lck or CD3ξ. RAGE KO cells produced less IL-2 when activated with anti-CD3 +/- anti-CD28. Stimulation with PMA restored signaling and (with ionomycin) IL-2 production. Silencing RAGE with siRNA also decreased signaling. Our studies show that RAGE expression in human T cells is associated with an activated signaling cascade. These findings suggest a link between inflammatory products that are found in patients with diabetes, other autoimmune diseases, and inflammation that may enhance T cell reactivity.

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