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Sci Rep. 2015 Mar 10;5:8959. doi: 10.1038/srep08959.

Tuning IL-2 signaling by ADP-ribosylation of CD25.

Author information

1
Institute of Immunology, University Medical Center, 20246 Hamburg, Germany.
2
Department of Clinical Chemistry, University Medical Center, 20246 Hamburg, Germany.
3
1] Institute of Immunology, University Medical Center, 20246 Hamburg, Germany [2] Department of Radiology, University Medical Center, 20246 Hamburg, Germany.
4
1] Normandy University, Institute for Research and Innovation in Biomedicine, 76183 Rouen, France [2] Inserm, U905, 76000 Rouen, France [3] Rouen University Hospital, Department of Immunology, 76000 Rouen, France.
5
1] Normandy University, Institute for Research and Innovation in Biomedicine, 76183 Rouen, France [2] Inserm, U905, 76000 Rouen, France.
6
1] Institute of Immunology, University Medical Center, 20246 Hamburg, Germany [2] Normandy University, Institute for Research and Innovation in Biomedicine, 76183 Rouen, France.

Abstract

Control of immunologic tolerance and homeostasis rely on Foxp3(+)CD4(+)CD25(+) 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.

PMID:
25753532
PMCID:
PMC4354014
DOI:
10.1038/srep08959
[Indexed for MEDLINE]
Free PMC Article

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