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Tuning IL-2 signaling by ADP-ribosylation of CD25

Abstract : Control of immunologic tolerance and homeostasis rely on Foxp3 1 CD4 1 CD25 1 regulatory T cells (Tregs) that constitutively express the high affinity receptor for Interleukin-2, CD25. Tregs proliferate in response to injections of IL-2/anti-IL-2 antibody complexes or low doses of IL-2. However, little is known about endogenous mechanisms that regulate the sensitivity of CD25 to signaling by IL-2. Here we demonstrate that CD25 is ADP-ribosylated at Arg35 in the IL-2 binding site by ecto-ADP-ribosyltransferase ARTC2.2, a toxin-related GPI-anchored ecto-enzyme. ADP-ribosylation inhibits binding of IL-2 by CD25, IL-2-induced phosphorylation of STAT5, and IL-2-dependent cell proliferation. Our study elucidates an as-yet-unrecognized mechanism to tune IL-2 signaling. This newly found mechanism might thwart Tregs at sites of inflammation and thereby permit a more potent response of activated effector T cells.
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Sophie Teege, Alexander Hann, Maria Miksiewicz, Cary Macmillan, Björn Rissiek, et al.. Tuning IL-2 signaling by ADP-ribosylation of CD25. Scientific Reports, Nature Publishing Group, 2015, 5 (1), ⟨10.1038/srep08959⟩. ⟨hal-02376180⟩

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