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

  • Metabolism. 2014 Oct;63(10):1272-9. doi: 10.1016/j.metabol.2014.06.010.
Silvana Cassano  1 ,  Valentina Pucino  2 ,  Claudia La Rocca  3 ,  Claudio Procaccini  1 ,  Veronica De Rosa  4 ,  Gianni Marone  5 ,  Giuseppe Matarese  6
Affiliations
  • 1. Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Napoli, Italy.
  • 2. Dipartimento di Scienze Mediche Traslazionali, Università di Napoli "Federico II", 80131 Napoli, Italy.
  • 3. Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Napoli, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II", 80131 Napoli, Italy.
  • 4. Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Napoli, Italy; Unità di NeuroImmunologia, IRCCS-Fondazione Santa Lucia, 00143 Roma, Italy.
  • 5. Dipartimento di Scienze Mediche Traslazionali, Università di Napoli "Federico II", 80131 Napoli, Italy; Centro Interdipartimentale di Ricerca in Scienze Immunologiche di Base e Cliniche (CISI), Università di Napoli "Federico II", 80131 Napoli, Italy.
  • 6. Dipartimento di Medicina e Chirurgia, Facoltà di Medicina e Chirurgia, Università di Salerno, Baronissi Campus, 84081 Baronissi, Salerno, Italy; IRCCS-MultiMedica, 20138 Milano, Italy. Electronic address: [email protected].
PMID: 25060689 DOI: 10.1016/j.metabol.2014.06.010
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.

Keywords
Autophagy; Leptin; Metabolism; T cells; mTOR.