| First Author | Katholnig K | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 4 | Pages | 1519-27 |
| PubMed ID | 23315073 | Mgi Jnum | J:193238 |
| Mgi Id | MGI:5468028 | Doi | 10.4049/jimmunol.1202683 |
| Citation | Katholnig K, et al. (2013) p38alpha Senses Environmental Stress To Control Innate Immune Responses via Mechanistic Target of Rapamycin. J Immunol 190(4):1519-27 |
| abstractText | The MAPK p38alpha senses environmental stressors and orchestrates inflammatory and immunomodulatory reactions. However, the molecular mechanism how p38alpha controls immunomodulatory responses in myeloid cells remains elusive. We found that in monocytes and macrophages, p38alpha activated the mechanistic target of rapamycin (mTOR) pathway in vitro and in vivo. p38alpha signaling in myeloid immune cells promoted IL-10 but inhibited IL-12 expression via mTOR and blocked the differentiation of proinflammatory CD4(+) Th1 cells. Cellular stress induced p38alpha-mediated mTOR activation that was independent of PI3K but dependent on the MAPK-activated protein kinase 2 and on the inhibition of tuberous sclerosis 1 and 2, a negative regulatory complex of mTOR signaling. Remarkably, p38alpha and PI3K concurrently modulated mTOR to balance IL-12 and IL-10 expression. Our data link p38alpha to mTOR signaling in myeloid immune cells that is decisive for tuning the immune response in dependence on the environmental milieu. |
