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.

IFNgammaR2 trafficking tunes IFNgamma-STAT1 signaling in T lymphocytes

REGIS, GABRIELLA;CONTI, Laura;NOVELLI, Francesco
2006

Abstract

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.
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http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W7H-4HWXM21-1&_user=525216&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000026382&_version=1&_urlVersion=0&_userid=525216&md5=20d3d1aa60bf96d6997c6b90f3ffa0d8
T cell; IFN-gamma receptor; IFN-gamma signaling; apoptosis
G. REGIS; L. CONTI; D. BOSELLI; F. NOVELLI
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/37146
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