IFNgammaR2 trafficking tunes IFNgamma-STAT1 signaling in T lymphocytes.
Ligand-dependent downregulation of the interferon gamma receptor signaling chain (IFNgammaR2) has always been seen as a key mechanism for shielding T lymphocytes from the antiproliferative effects of the IFNgamma-signal transducer and activator of transcription 1 (STAT1) pathway. Now, however, a ligand-independent mechanism of IFNgammaR2 internalization is emerging as a more general way of limiting IFNgamma-STAT1 signaling in T cells, with insulin-like growth factor-1 (IGF-1) and iron as the main players. Here, we review the array of immunomodulatory effects exerted by these two factors on different cell types involved in the immune response; these effects suggest that an inflammatory environment generates signals that favor IFNgammaR2 cell-surface accumulation and IFNgamma-induced apoptosis in T cells, whereas an anti-inflammatory environment promotes IFNgammaR2 internalization and induces T cell unresponsiveness to IFNgamma signaling.
Regis
Gabriella
G
Center for Experimental Research and Medical Studies (CERMS), San Giovanni Battista Hospital, Via Santena 5, I-10126 Turin, Italy.
Conti
Laura
L
Boselli
Daniela
D
Novelli
Francesco
F
D000818:Animals; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism*; D021381:Protein Transport; D017471:Receptors, Interferon / Q000276:immunology* / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D000096743:Interferon gamma Receptor