Abstract
Objective In this report we show that the adipocytokine leptin directly modulates autophagy in human CD4+CD25- conventional (Tconv) T cells.
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.
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.
Original language | English |
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Pages (from-to) | 1272-1279 |
Number of pages | 8 |
Journal | Metabolism |
Volume | 63 |
Issue number | 10 |
DOIs | |
Publication status | Published - Oct 1 2014 |
Keywords
- Autophagy
- Leptin
- Metabolism
- mTOR
- T cells
ASJC Scopus subject areas
- Endocrinology
- Endocrinology, Diabetes and Metabolism