Tuning IL-2 signaling by ADP-ribosylation of CD25.
Sci Rep
; 5: 8959, 2015 Mar 10.
Article
de En
| MEDLINE
| ID: mdl-25753532
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Interleukine-2
/
Lymphocytes T régulateurs
/
Sous-unité alpha du récepteur à l'interleukine-2
/
Tolérance immunitaire
Limites:
Animals
/
Humans
Langue:
En
Journal:
Sci Rep
Année:
2015
Type de document:
Article
Pays d'affiliation:
Allemagne