Genomics

Dataset Information

0

The TSC/mTOR pathway regulates the innate inflammatory response


ABSTRACT: The TSC/mTOR (tuberous sclerosis complex/mammalian target of rapamycin) pathway has a central role in cell growth and is involved in human tumorigenesis. Here, we demonstrate an unexpected role of TSC2 and mTOR in regulating key inflammatory cytokines in monocytes, macrophages, and dendritic cells after bacterial stimulation. mTOR deficiency promoted IL-12/IL-23 and blocked IL-10 production via the transcription factor NF-kB. Conversely, loss of TSC2, a key negative regulator of mTOR, led to reduced NF-kB activity, limited IL-12 but enhanced IL-10 production. Transcriptional profiling demonstrated that mTOR additionally regulated many mediators important for inflammation and immunoregulation including PD-L1, CCR5, CCL22, and MCP-1. mTOR inhibition in vivo rescued susceptible mice from a lethal Listeria monocytogenes infection by modulating IL-12/IL-10 production. These data identify the TSC2/mTOR pathway as a novel pathway in innate immune responses by controlling NF-kB with profound clinical implications for infectious diseases, cancer, or transplantation. Keywords: inflammatory response of monocytes to LPS and rapamycin

ORGANISM(S): Homo sapiens

PROVIDER: GSE6002 | GEO | 2008/09/30

SECONDARY ACCESSION(S): PRJNA97791

REPOSITORIES: GEO

Similar Datasets

| E-GEOD-6002 | biostudies-arrayexpress
| E-GEOD-27982 | biostudies-arrayexpress
| E-GEOD-21755 | biostudies-arrayexpress
| 2696263 | ecrin-mdr-crc
2020-03-21 | GSE106828 | GEO
| E-GEOD-28021 | biostudies-arrayexpress
2011-08-03 | GSE27982 | GEO
2011-08-03 | GSE28021 | GEO
2009-10-21 | GSE16944 | GEO
2015-12-31 | GSE70146 | GEO