Unravelling paradoxes in regulatory T cell biology: the molecular basis for an mTOR - dependent oscillatory metabolic switch controlling immune tolerance and autoimmunity (DSB.AD001.052)
Area tematica
Area progettuale
Oncologia e Immunologia (DSB.AD001)Struttura responsabile del progetto di ricerca
Istituto per l'endocrinologia e l'oncologia "Gaetano Salvatore" (IEOS)
Responsabile di progetto
GIUSEPPE MATARESE
Telefono: 0817464580
E-mail: giuseppe.matarese@cnr.it
Abstract
Our group has been investigating how the nutrient/energy-sensing mammalian target of rapamycin (mTOR)-pathway affects the responsiveness of CD4+CD25+FoxP3+ regulatory T cells (Tregs). We have shown that Tregs have a high metabolic profile associated with the hyperactivation of the mTORpathway,responsible for their in vitro anergy. A transient mTOR inhibition induced Tregs proliferation in the absence of exogenous interleukin-2 (IL-2), but proliferating Tregs increased the levels of mTOR activation to sustain their own expansion. These data indicated that the metabolic state influences Tregs fate and the responsiveness to TCR stimulation in a dynamic/oscillatory fashion through the mTOR-pathway. The results also suggested a new mechanism of regulation between metabolism and immune tolerance in the Tregs in which mTOR could be activated under physiological conditions in response to changes of the energy status. In this project, we intend to further dissect the relationship between mTOR oscillating activity and Tregs responsiveness, unravelling important questions on the biology of Tregs for furthering the understanding of basic mechanisms governing immune tolerance and autoimmunity.
Obiettivi
L'obiettivo generale è rivolto alla comprensione dei meccanismi patogenetici delle malattie infiammatorie croniche ad eziologie autoimmunitaria. L'obiettivo specifico è dato dallo studio della leptina, proteina simile alle citochine prodotta dal tessuto adiposo, come elemento comune coinvolto nella patogenesi di sclerosi multipla, diabete autoimmunitario e infiammazione legata all'obesità.
Data inizio attività
01/01/2013
Parole chiave
mTOR, leptin, Treg cells
Ultimo aggiornamento: 16/04/2024