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.

Leptin modulates autophagy in human CD4+CD25− conventional T cells

Cassano, Silvana;La Rocca, Claudia;Procaccini, Claudio;De Rosa, Veronica;Marone, Gianni;Matarese, Giuseppe
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.
2014
Istituto di Endocrinologia e Oncologia Sperimentale ''G. Salvatore'' - IEOS
Autophagy
Leptin
Metabolism
T cells
mTOR
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/485623
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