{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:11:36Z","timestamp":1790025096032,"version":"4.0.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The MAPK p38\u03b1 senses environmental stressors and orchestrates inflammatory and immunomodulatory reactions. However, the molecular mechanism how p38\u03b1 controls immunomodulatory responses in myeloid cells remains elusive. We found that in monocytes and macrophages, p38\u03b1 activated the mechanistic target of rapamycin (mTOR) pathway in vitro and in vivo. p38\u03b1 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 p38\u03b1-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, p38\u03b1 and PI3K concurrently modulated mTOR to balance IL-12 and IL-10 expression. Our data link p38\u03b1 to mTOR signaling in myeloid immune cells that is decisive for tuning the immune response in dependence on the environmental milieu.<\/jats:p>","DOI":"10.4049\/jimmunol.1202683","type":"journal-article","created":{"date-parts":[[2013,1,12]],"date-time":"2013-01-12T06:45:04Z","timestamp":1357973104000},"page":"1519-1527","source":"Crossref","is-referenced-by-count":31,"title":["p38\u03b1 Senses Environmental Stress To Control Innate Immune Responses via Mechanistic Target of Rapamycin"],"prefix":"10.1093","volume":"190","author":[{"given":"Karl","family":"Katholnig","sequence":"first","affiliation":[{"name":"Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna , 1090 Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C","family":"Kaltenecker","sequence":"additional","affiliation":[{"name":"Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna , 1090 Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margit","family":"Rosner","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, Medical University of Vienna , 1090 Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Lassnig","sequence":"additional","affiliation":[{"name":"Institute of Animal Breeding and Genetics and Biomodels Austria, University of Veterinary Medicine Vienna , 1210 Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard J","family":"Zlabinger","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Medical University of Vienna , 1090 Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Gaestel","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry, Hannover Medical School , 30625 Hannover,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Animal Breeding and Genetics and Biomodels Austria, University of Veterinary Medicine Vienna , 1210 Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hengstschl\u00e4ger","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, Medical University of Vienna , 1090 Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter H","family":"H\u00f6rl","sequence":"additional","affiliation":[{"name":"Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna , 1090 Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Mo","family":"Park","sequence":"additional","affiliation":[{"name":"Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus D","family":"S\u00e4emann","sequence":"additional","affiliation":[{"name":"Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna , 1090 Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Weichhart","sequence":"additional","affiliation":[{"name":"Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna , 1090 Vienna,","place":["Austria"]},{"name":"Institute of Medical Genetics, Medical University of Vienna , 1090 Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,2,15]]},"reference":[{"key":"2025032406344483300_r1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. 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