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. 2008 Oct 17;29(4):565-77.
doi: 10.1016/j.immuni.2008.08.012. Epub 2008 Oct 9.

The TSC-mTOR signaling pathway regulates the innate inflammatory response (VSports app下载)

Thomas Weichhart  1 , Giuseppina Costantino, Marko Poglitsch, Margit Rosner, Maximilian Zeyda, Karl M Stuhlmeier, Thomas Kolbe, Thomas M Stulnig, Walter H Hörl, Markus Hengstschläger, Mathias Müller, Marcus D Säemann
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Free article

The TSC-mTOR signaling pathway regulates the innate inflammatory response

Thomas Weichhart et al. Immunity. .
Free article

Abstract

The innate inflammatory immune response must be tightly controlled to avoid damage to the host. Here, we showed that the tuberous sclerosis complex-mammalian target of rapamycin (TSC-mTOR) pathway regulated inflammatory responses after bacterial stimulation in monocytes, macrophages, and primary dendritic cells. Inhibition of mTOR by rapamycin promoted production of proinflammatory cytokines via the transcription factor NF-kappaB but blocked the release of interleukin-10 via the transcription factor STAT3. Conversely, deletion of TSC2, the key negative regulator of mTOR, diminished NF-kappaB but enhanced STAT3 activity and reversed this proinflammatory cytokine shift. Rapamycin-hyperactivated monocytes displayed a strong T helper 1 (Th1) cell- and Th17 cell-polarizing potency. Inhibition of mTOR in vivo regulated the inflammatory response and protected genetically susceptible mice against lethal Listeria monocytogenes infection. These data identify the TSC2-mTOR pathway as a key regulator of innate immune homeostasis with broad clinical implications for infectious and autoimmune diseases, vaccination, cancer, and transplantation. VSports手机版.

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