| First Author | Weichhart T | Year | 2008 |
| Journal | Immunity | Volume | 29 |
| Issue | 4 | Pages | 565-77 |
| PubMed ID | 18848473 | Mgi Jnum | J:141115 |
| Mgi Id | MGI:3815386 | Doi | 10.1016/j.immuni.2008.08.012 |
| Citation | Weichhart T, et al. (2008) The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity 29(4):565-77 |
| abstractText | 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. |
