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Leptin-induced mTOR activation defines a specific molecular and transcriptional signature controlling CD4+ effector T cell responses.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2012 Sep 15; Vol. 189 (6), pp. 2941-53. Date of Electronic Publication: 2012 Aug 17. - Publication Year :
- 2012
-
Abstract
- The sensing by T cells of metabolic and energetic changes in the microenvironment can determine the differentiation, maturation, and activation of these cells. Although it is known that mammalian target of rapamycin (mTOR) gauges nutritonal and energetic signals in the extracellular milieu, it is not known how mTOR and metabolism influence CD4+CD25-FOXP3- effector T cell (Teff) responses. In this article, we show that leptin-induced activation of mTOR, which, in turn, controls leptin production and signaling, causes a defined cellular, biochemical, and transcriptional signature that determine the outcome of Teff responses, both in vitro and in vivo. The blockade of leptin/leptin receptor signaling, induced by genetic means or by starvation, leads to impaired mTOR activity that inhibits the proliferation of Teffs in vivo. Notably, the transcriptional signature of Teffs in the presence of leptin blockade appears similar to that observed in rapamycin-treated Teffs. These results identify a novel link between nutritional status and Teff responses through the leptin-mTOR axis and define a potential target for Teff modulation in normal and pathologic conditions.
- Subjects :
- Animals
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes pathology
Cell Line
Cells, Cultured
Down-Regulation drug effects
Down-Regulation genetics
Down-Regulation immunology
Enzyme Activation drug effects
Enzyme Activation immunology
Female
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Obese
Mice, Transgenic
Sirolimus pharmacology
TOR Serine-Threonine Kinases antagonists & inhibitors
Transcriptional Activation drug effects
CD4-Positive T-Lymphocytes immunology
Leptin physiology
TOR Serine-Threonine Kinases metabolism
Transcriptional Activation immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 189
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 22904304
- Full Text :
- https://doi.org/10.4049/jimmunol.1200935