Data di Pubblicazione:
2014
Abstract:
OBJECTIVE:
In this report we show that the adipocytokine leptin directly modulates autophagy in human CD4(+)CD25(-) conventional (Tconv) T cells.
RESULTS:
In vitro treatment with recombinant human leptin determined an inhibition of autophagy during T cell receptor (TCR) stimulation, and this phenomenon was dose- and time-dependent. The events were secondary to the activation of the mammalian-target of rapamycin (mTOR)-pathway induced by leptin, as testified by its reversion induced by mTOR inhibition with rapamycin. At molecular level these phenomena associated with Bcl-2 up-regulation and its interaction with Beclin-1, whose complex exerts a negative effect on autophagy.
MATERIALS/METHODS:
The impact of leptin on autophagy of Tconv cells was determined at biochemical level by western blotting and by flow cytometry; the interaction between BCL-2 and Beclin-1 by co-immunoprecipitation assays.
CONCLUSIONS:
Our results, suggest that in unconditioned, freshly-isolated human Tconv cells, autophagy and proliferation are controlled by leptin during TCR-engagement, and that both phenomena occur alternatively indicating a balance between these processes during immune activation.
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
In this report we show that the adipocytokine leptin directly modulates autophagy in human CD4(+)CD25(-) conventional (Tconv) T cells.
RESULTS:
In vitro treatment with recombinant human leptin determined an inhibition of autophagy during T cell receptor (TCR) stimulation, and this phenomenon was dose- and time-dependent. The events were secondary to the activation of the mammalian-target of rapamycin (mTOR)-pathway induced by leptin, as testified by its reversion induced by mTOR inhibition with rapamycin. At molecular level these phenomena associated with Bcl-2 up-regulation and its interaction with Beclin-1, whose complex exerts a negative effect on autophagy.
MATERIALS/METHODS:
The impact of leptin on autophagy of Tconv cells was determined at biochemical level by western blotting and by flow cytometry; the interaction between BCL-2 and Beclin-1 by co-immunoprecipitation assays.
CONCLUSIONS:
Our results, suggest that in unconditioned, freshly-isolated human Tconv cells, autophagy and proliferation are controlled by leptin during TCR-engagement, and that both phenomena occur alternatively indicating a balance between these processes during immune activation.
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Tipologia CRIS:
01.01 Articolo in rivista
Keywords:
Autophagy; Leptin; Metabolism; mTOR; T cells
Elenco autori:
LA ROCCA, Claudia; Pucino, Valentina; Matarese, Giuseppe; DE ROSA, Veronica; Procaccini, Claudio; Cassano, Silvana
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