1. Leptin modulates autophagy in human CD4(+)CD25(-) conventional T cells
- Author
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Claudio Procaccini, Valentina Pucino, Giuseppe Matarese, Gianni Marone, Silvana Cassano, Claudia La Rocca, Veronica De Rosa, Cassano, S., Pucino, V., La Rocca, C., Procaccini, C., De Rosa, V., Marone, Gianni, and Matarese, Giuseppe
- Subjects
CD4-Positive T-Lymphocytes ,hLepRb, human leptin receptor-b ,Leptin ,Endocrinology, Diabetes and Metabolism ,Endocrinology ,Receptors ,Sirolimu ,Membrane Protein ,Apoptosis Regulatory Protein ,TOR Serine-Threonine Kinase ,TCR, T cell receptor ,LC3-II, microtubule associated protein light chain 3-II ,TOR Serine-Threonine Kinases ,digestive, oral, and skin physiology ,Clinical Science ,Tconv, T conventional ,Cell biology ,Up-Regulation ,Proto-Oncogene Proteins c-bcl-2 ,CD4-Positive T-Lymphocyte ,mTOR, mammalian-target of rapamycin ,Antigen ,mTOR ,Beclin-1 ,Signal transduction ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,Human ,Receptor ,Signal Transduction ,Receptors, Antigen, T-Cell ,T cells ,Biology ,Cell Line ,Downregulation and upregulation ,medicine ,Autophagy ,Humans ,Immunoprecipitation ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Sirolimus ,Cell growth ,Interleukin-2 Receptor alpha Subunit ,Membrane Proteins ,T cell ,T-Cell ,Metabolism ,Apoptosis Regulatory Proteins ,Cell culture - 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.
- Published
- 2014