{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:43:09Z","timestamp":1791308589508,"version":"4.3.1"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/ncomms5696","type":"journal-article","created":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T06:44:25Z","timestamp":1409553865000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":274,"title":["TSC1 controls macrophage polarization to prevent inflammatory disease"],"prefix":"10.1038","volume":"5","author":[{"given":"Linnan","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longjie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhu","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelian","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianjun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongling","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingjie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxia","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongzhou","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianfeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,9,1]]},"reference":[{"key":"BFncomms5696_CR1","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1038\/ni.2109","volume":"12","author":"SJ Galli","year":"2011","unstructured":"Galli, S. J., Borregaard, N. & Wynn, T. A. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat. Immunol. 12, 1035\u20131044 (2011).","journal-title":"Nat. Immunol."},{"key":"BFncomms5696_CR2","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/nri3073","volume":"11","author":"PJ Murray","year":"2011","unstructured":"Murray, P. J. & Wynn, T. A. Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol. 11, 723\u2013737 (2011).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms5696_CR3","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1038\/nri2448","volume":"8","author":"DM Mosser","year":"2008","unstructured":"Mosser, D. M. & Edwards, J. P. Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 8, 958\u2013969 (2008).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms5696_CR4","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.cell.2007.08.009","volume":"130","author":"JC Paulson","year":"2007","unstructured":"Paulson, J. C. Innate immune response triggers lupus-like autoimmune disease. Cell 130, 589\u2013591 (2007).","journal-title":"Cell"},{"key":"BFncomms5696_CR5","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.immuni.2007.06.008","volume":"27","author":"RS Green","year":"2007","unstructured":"Green, R. S. et al. Mammalian N-glycan branching protects against innate immune self-recognition and inflammation in autoimmune disease pathogenesis. Immunity 27, 308\u2013320 (2007).","journal-title":"Immunity"},{"key":"BFncomms5696_CR6","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1084\/jem.183.2.371","volume":"183","author":"CC Yu","year":"1996","unstructured":"Yu, C. C. et al. B and T cells are not required for the viable motheaten phenotype. J. Exp. Med. 183, 371\u2013380 (1996).","journal-title":"J. Exp. Med."},{"key":"BFncomms5696_CR7","doi-asserted-by":"publisher","first-page":"14978","DOI":"10.1073\/pnas.0809784106","volume":"106","author":"C Porta","year":"2009","unstructured":"Porta, C. et al. Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proc. Natl Acad. Sci. USA 106, 14978\u201314983 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms5696_CR8","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.immuni.2005.09.003","volume":"23","author":"MJ Rauh","year":"2005","unstructured":"Rauh, M. J. et al. SHIP represses the generation of alternatively activated macrophages. Immunity 23, 361\u2013374 (2005).","journal-title":"Immunity"},{"key":"BFncomms5696_CR9","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1038\/nri3088","volume":"11","author":"T Lawrence","year":"2011","unstructured":"Lawrence, T. & Natoli, G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat. Rev. Immunol. 11, 750\u2013761 (2011).","journal-title":"Nat. Rev. Immunol."},{"key":"BFncomms5696_CR10","doi-asserted-by":"publisher","first-page":"2397","DOI":"10.1084\/jem.20081297","volume":"205","author":"C Chen","year":"2008","unstructured":"Chen, C. et al. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J. Exp. Med. 205, 2397\u20132408 (2008).","journal-title":"J. Exp. Med."},{"key":"BFncomms5696_CR11","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/ng1494","volume":"37","author":"K Inoki","year":"2005","unstructured":"Inoki, K., Corradetti, M. N. & Guan, K. L. Dysregulation of the TSC-mTOR pathway in human disease. Nat. Genet. 37, 19\u201324 (2005).","journal-title":"Nat. Genet."},{"key":"BFncomms5696_CR12","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1038\/ni.2068","volume":"12","author":"K Yang","year":"2011","unstructured":"Yang, K., Neale, G., Green, D. R., He, W. & Chi, H. The tumor suppressor Tsc1 enforces quiescence of naive T cells to promote immune homeostasis and function. Nat. Immunol. 12, 888\u2013897 (2011).","journal-title":"Nat. Immunol."},{"key":"BFncomms5696_CR13","doi-asserted-by":"publisher","first-page":"e30592","DOI":"10.1371\/journal.pone.0030592","volume":"7","author":"L Zhang","year":"2012","unstructured":"Zhang, L. et al. TSC1\/2 signaling complex is essential for peripheral naive CD8+ T cell survival and homeostasis in mice. PLoS ONE 7, e30592 (2012).","journal-title":"PLoS ONE"},{"key":"BFncomms5696_CR14","doi-asserted-by":"publisher","first-page":"8313","DOI":"10.1074\/jbc.C500451200","volume":"281","author":"H Chong-Kopera","year":"2006","unstructured":"Chong-Kopera, H. et al. TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase. J. Biol. Chem. 281, 8313\u20138316 (2006).","journal-title":"J. Biol. Chem."},{"key":"BFncomms5696_CR15","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","volume":"124","author":"S Wullschleger","year":"2006","unstructured":"Wullschleger, S., Loewith, R. & Hall, M. N. TOR signaling in growth and metabolism. Cell 124, 471\u2013484 (2006).","journal-title":"Cell"},{"key":"BFncomms5696_CR16","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1038\/ncb839","volume":"4","author":"K Inoki","year":"2002","unstructured":"Inoki, K., Li, Y., Zhu, T., Wu, J. & Guan, K. L. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat. Cell Biol. 4, 648\u2013657 (2002).","journal-title":"Nat. Cell Biol."},{"key":"BFncomms5696_CR17","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1038\/ncb999","volume":"5","author":"Y Zhang","year":"2003","unstructured":"Zhang, Y. et al. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat. Cell Biol. 5, 578\u2013581 (2003).","journal-title":"Nat. Cell Biol."},{"key":"BFncomms5696_CR18","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1101\/gad.1110003","volume":"17","author":"K Inoki","year":"2003","unstructured":"Inoki, K., Li, Y., Xu, T. & Guan, K. L. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev. 17, 1829\u20131834 (2003).","journal-title":"Genes Dev."},{"key":"BFncomms5696_CR19","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1126\/science.1106148","volume":"307","author":"DD Sarbassov","year":"2005","unstructured":"Sarbassov, D. D., Guertin, D. A., Ali, S. M. & Sabatini, D. M. Phosphorylation and regulation of Akt\/PKB by the rictor-mTOR complex. Science 307, 1098\u20131101 (2005).","journal-title":"Science"},{"key":"BFncomms5696_CR20","doi-asserted-by":"publisher","first-page":"4104","DOI":"10.1128\/MCB.00289-08","volume":"28","author":"J Huang","year":"2008","unstructured":"Huang, J., Dibble, C. C., Matsuzaki, M. & Manning, B. D. The TSC1-TSC2 complex is required for proper activation of mTOR complex 2. Mol. Cell Biol. 28, 4104\u20134115 (2008).","journal-title":"Mol. Cell Biol."},{"key":"BFncomms5696_CR21","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1038\/ncb840","volume":"4","author":"CJ Potter","year":"2002","unstructured":"Potter, C. J., Pedraza, L. G. & Xu, T. Akt regulates growth by directly phosphorylating Tsc2. Nat. Cell Biol. 4, 658\u2013665 (2002).","journal-title":"Nat. Cell Biol."},{"key":"BFncomms5696_CR22","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1046\/j.1600-6143.2004.00673.x","volume":"5","author":"T Taner","year":"2005","unstructured":"Taner, T., Hackstein, H., Wang, Z., Morelli, A. E. & Thomson, A. W. Rapamycin-treated, alloantigen-pulsed host dendritic cells induce ag-specific T cell regulation and prolong graft survival. Am. J. Transplant. 5, 228\u2013236 (2005).","journal-title":"Am. J. Transplant."},{"key":"BFncomms5696_CR23","doi-asserted-by":"publisher","first-page":"3919","DOI":"10.4049\/jimmunol.1000296","volume":"185","author":"M Haidinger","year":"2010","unstructured":"Haidinger, M. et al. A versatile role of mammalian target of rapamycin in human dendritic cell function and differentiation. J. Immunol. 185, 3919\u20133931 (2010).","journal-title":"J. Immunol."},{"key":"BFncomms5696_CR24","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1182\/blood-2008-02-137430","volume":"112","author":"M Ohtani","year":"2008","unstructured":"Ohtani, M. et al. Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharide-induced interleukin-12 production in dendritic cells. Blood 112, 635\u2013643 (2008).","journal-title":"Blood"},{"key":"BFncomms5696_CR25","doi-asserted-by":"publisher","first-page":"4736","DOI":"10.4049\/jimmunol.1200069","volume":"188","author":"M Ohtani","year":"2012","unstructured":"Ohtani, M. et al. Cutting edge: mTORC1 in intestinal CD11c+ CD11b+ dendritic cells regulates intestinal homeostasis by promoting IL-10 production. J. Immunol. 188, 4736\u20134740 (2012).","journal-title":"J. Immunol."},{"key":"BFncomms5696_CR26","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.4049\/jimmunol.1103741","volume":"189","author":"E Amiel","year":"2012","unstructured":"Amiel, E. et al. Inhibition of mechanistic target of rapamycin promotes dendritic cell activation and enhances therapeutic autologous vaccination in mice. J. Immunol. 189, 2151\u20132158 (2012).","journal-title":"J. Immunol."},{"key":"BFncomms5696_CR27","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1111\/j.1462-5822.2006.00699.x","volume":"8","author":"CS Yang","year":"2006","unstructured":"Yang, C. S. et al. Intracellular network of phosphatidylinositol 3-kinase, mammalian target of the rapamycin\/70 kDa ribosomal S6 kinase 1, and mitogen-activated protein kinases pathways for regulating mycobacteria-induced IL-23 expression in human macrophages. Cell Microbiol. 8, 1158\u20131171 (2006).","journal-title":"Cell Microbiol."},{"key":"BFncomms5696_CR28","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.immuni.2008.08.012","volume":"29","author":"T Weichhart","year":"2008","unstructured":"Weichhart, T. et al. The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity 29, 565\u2013577 (2008).","journal-title":"Immunity"},{"key":"BFncomms5696_CR29","doi-asserted-by":"publisher","first-page":"4273","DOI":"10.1182\/blood-2010-09-310888","volume":"117","author":"T Weichhart","year":"2011","unstructured":"Weichhart, T. et al. Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells. Blood 117, 4273\u20134283 (2011).","journal-title":"Blood"},{"key":"BFncomms5696_CR30","doi-asserted-by":"publisher","first-page":"2604","DOI":"10.1111\/j.1600-6143.2010.03302.x","volume":"10","author":"S Brouard","year":"2010","unstructured":"Brouard, S. et al. Comparative transcriptional and phenotypic peripheral blood analysis of kidney recipients under cyclosporin A or sirolimus monotherapy. Am. J. Transplant. 10, 2604\u20132614 (2010).","journal-title":"Am. J. Transplant."},{"key":"BFncomms5696_CR31","doi-asserted-by":"publisher","first-page":"3658","DOI":"10.4049\/jimmunol.1102187","volume":"188","author":"H Pan","year":"2012","unstructured":"Pan, H., O'Brien, T. F., Zhang, P. & Zhong, X. P. The role of tuberous sclerosis complex 1 in regulating innate immunity. J. Immunol. 188, 3658\u20133666 (2012).","journal-title":"J. Immunol."},{"key":"BFncomms5696_CR32","doi-asserted-by":"publisher","first-page":"2834","DOI":"10.1038\/ncomms3834","volume":"4","author":"V Byles","year":"2013","unstructured":"Byles, V. et al. The TSC-mTOR pathway regulates macrophage polarization. Nat. Commun. 4, 2834 (2013).","journal-title":"Nat. Commun."},{"key":"BFncomms5696_CR33","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1038\/ni.1671","volume":"9","author":"KC El Kasmi","year":"2008","unstructured":"El Kasmi, K. C. et al. Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens. Nat. Immunol. 9, 1399\u20131406 (2008).","journal-title":"Nat. Immunol."},{"key":"BFncomms5696_CR34","doi-asserted-by":"publisher","first-page":"5618","DOI":"10.1158\/0008-5472.CAN-06-0364","volume":"66","author":"MJ Riemenschneider","year":"2006","unstructured":"Riemenschneider, M. J., Betensky, R. A., Pasedag, S. M. & Louis, D. N. AKT activation in human glioblastomas enhances proliferation via TSC2 and S6 kinase signaling. Cancer Res. 66, 5618\u20135623 (2006).","journal-title":"Cancer Res."},{"key":"BFncomms5696_CR35","doi-asserted-by":"publisher","first-page":"9517","DOI":"10.1073\/pnas.1119038109","volume":"109","author":"A Arranz","year":"2012","unstructured":"Arranz, A. et al. Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization. Proc. Natl Acad. Sci. USA 109, 9517\u20139522 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms5696_CR36","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1038\/ni986","volume":"4","author":"M Yamamoto","year":"2003","unstructured":"Yamamoto, M. et al. TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat. Immunol. 4, 1144\u20131150 (2003).","journal-title":"Nat. Immunol."},{"key":"BFncomms5696_CR37","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1016\/j.cellsig.2012.01.018","volume":"24","author":"JG Bode","year":"2012","unstructured":"Bode, J. G., Ehlting, C. & Haussinger, D. The macrophage response towards LPS and its control through the p38(MAPK)-STAT3 axis. Cell Signal. 24, 1185\u20131194 (2012).","journal-title":"Cell Signal."},{"key":"BFncomms5696_CR38","doi-asserted-by":"publisher","first-page":"40406","DOI":"10.1074\/jbc.M508361200","volume":"280","author":"RC Hresko","year":"2005","unstructured":"Hresko, R. C. & Mueckler, M. mTOR.RICTOR is the Ser473 kinase for Akt\/protein kinase B in 3T3-L1 adipocytes. J. Biol. Chem. 280, 40406\u201340416 (2005).","journal-title":"J. Biol. Chem."},{"key":"BFncomms5696_CR39","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.tibs.2003.09.003","volume":"28","author":"BD Manning","year":"2003","unstructured":"Manning, B. D. & Cantley, L. C. Rheb fills a GAP between TSC and TOR. Trends Biochem. Sci. 28, 573\u2013576 (2003).","journal-title":"Trends Biochem. Sci."},{"key":"BFncomms5696_CR40","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1172\/JCI59643","volume":"122","author":"A Sica","year":"2012","unstructured":"Sica, A. & Mantovani, A. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest. 122, 787\u2013795 (2012).","journal-title":"J. Clin. Invest."},{"key":"BFncomms5696_CR41","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.gene.2005.04.004","volume":"353","author":"MJ Gray","year":"2005","unstructured":"Gray, M. J., Poljakovic, M., Kepka-Lenhart, D. & Morris, S. M. Jr Induction of arginase I transcription by IL-4 requires a composite DNA response element for STAT6 and C\/EBPbeta. Gene 353, 98\u2013106 (2005).","journal-title":"Gene"},{"key":"BFncomms5696_CR42","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1097\/SHK.0b013e3181f0e7a3","volume":"35","author":"HB Hsiao","year":"2011","unstructured":"Hsiao, H. B., Wu, J. B., Lin, H. & Lin, W. C. Kinsenoside isolated from Anoectochilus formosanus suppresses LPS-stimulated inflammatory reactions in macrophages and endotoxin shock in mice. Shock 35, 184\u2013190 (2011).","journal-title":"Shock"},{"key":"BFncomms5696_CR43","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1165\/ajrcmb.27.2.4788","volume":"27","author":"EM Janssen","year":"2002","unstructured":"Janssen, E. M., Wauben, M. H., Nijkamp, F. P., van Eden, W. & van Oosterhout, A. J. Immunomodulatory effects of antigen-pulsed macrophages in a murine model of allergic asthma. Am. J. Respir. Cell Mol. Biol. 27, 257\u2013264 (2002).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"BFncomms5696_CR44","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1159\/000336025","volume":"4","author":"P Dasgupta","year":"2012","unstructured":"Dasgupta, P. & Keegan, A. D. Contribution of alternatively activated macrophages to allergic lung inflammation: a tale of mice and men. J. Innate Immun. 4, 478\u2013488 (2012).","journal-title":"J. Innate Immun."},{"key":"BFncomms5696_CR45","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.immuni.2010.05.007","volume":"32","author":"S Gordon","year":"2010","unstructured":"Gordon, S. & Martinez, F. O. Alternative activation of macrophages: mechanism and functions. Immunity 32, 593\u2013604 (2010).","journal-title":"Immunity"},{"key":"BFncomms5696_CR46","doi-asserted-by":"publisher","first-page":"32124","DOI":"10.1074\/jbc.M203298200","volume":"277","author":"M Guha","year":"2002","unstructured":"Guha, M. & Mackman, N. The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. J. Biol. Chem. 277, 32124\u201332132 (2002).","journal-title":"J. Biol. Chem."},{"key":"BFncomms5696_CR47","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.tibs.2011.03.006","volume":"36","author":"MC Mendoza","year":"2011","unstructured":"Mendoza, M. C., Er, E. E. & Blenis, J. The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem. Sci. 36, 320\u2013328 (2011).","journal-title":"Trends Biochem. Sci."},{"key":"BFncomms5696_CR48","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.1517\/14728222.2011.639361","volume":"16(Suppl 2)","author":"A De Luca","year":"2012","unstructured":"De Luca, A., Maiello, M. R., D'Alessio, A., Pergameno, M. & Normanno, N. The RAS\/RAF\/MEK\/ERK and the PI3K\/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin. Ther. Targets 16(Suppl 2), S17\u2013S27 (2012).","journal-title":"Expert Opin. Ther. Targets"},{"key":"BFncomms5696_CR49","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.jaci.2010.10.045","volume":"127","author":"BN Melgert","year":"2011","unstructured":"Melgert, B. N. et al. More alternative activation of macrophages in lungs of asthmatic patients. J. Allergy Clin. Immunol. 127, 831\u2013833 (2011).","journal-title":"J. Allergy Clin. Immunol."},{"key":"BFncomms5696_CR50","doi-asserted-by":"publisher","first-page":"17475","DOI":"10.1073\/pnas.0908641106","volume":"106","author":"D Ruffell","year":"2009","unstructured":"Ruffell, D. et al. A CREB-C\/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair. Proc. Natl Acad. Sci. USA 106, 17475\u201317480 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms5696_CR51","doi-asserted-by":"publisher","first-page":"5564","DOI":"10.4049\/jimmunol.164.11.5564","volume":"164","author":"AE Medvedev","year":"2000","unstructured":"Medvedev, A. E., Kopydlowski, K. M. & Vogel, S. N. Inhibition of lipopolysaccharide-induced signal transduction in endotoxin-tolerized mouse macrophages: dysregulation of cytokine, chemokine, and toll-like receptor 2 and 4 gene expression. J. Immunol. 164, 5564\u20135574 (2000).","journal-title":"J. Immunol."},{"key":"BFncomms5696_CR52","doi-asserted-by":"publisher","first-page":"E1070","DOI":"10.1073\/pnas.1106454108","volume":"108","author":"J Goto","year":"2011","unstructured":"Goto, J. et al. Regulable neural progenitor-specific Tsc1 loss yields giant cells with organellar dysfunction in a model of tuberous sclerosis complex. Proc. Natl Acad. Sci. USA 108, E1070\u2013E1079 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms5696_CR53","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1172\/JCI200317222","volume":"112","author":"H Zhang","year":"2003","unstructured":"Zhang, H. et al. Loss of Tsc1\/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR. J. Clin. Invest. 112, 1223\u20131233 (2003).","journal-title":"J. Clin. Invest."},{"key":"BFncomms5696_CR54","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.devcel.2006.08.013","volume":"11","author":"C Shiota","year":"2006","unstructured":"Shiota, C., Woo, J. T., Lindner, J., Shelton, K. D. & Magnuson, M. A. Multiallelic disruption of the rictor gene in mice reveals that mTOR complex 2 is essential for fetal growth and viability. Dev. Cell 11, 583\u2013589 (2006).","journal-title":"Dev. Cell"},{"key":"BFncomms5696_CR55","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1023\/A:1008942828960","volume":"8","author":"BE Clausen","year":"1999","unstructured":"Clausen, B. E., Burkhardt, C., Reith, W., Renkawitz, R. & Forster, I. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res. 8, 265\u2013277 (1999).","journal-title":"Transgenic Res."},{"key":"BFncomms5696_CR56","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s00109-008-0304-8","volume":"86","author":"H Ma","year":"2008","unstructured":"Ma, H. et al. Diabetes-induced alteration of F4\/80+ macrophages: a study in mice with streptozotocin-induced diabetes for a long term. J. Mol. Med. (Berl) 86, 391\u2013400 (2008).","journal-title":"J. Mol. Med. (Berl)"},{"key":"BFncomms5696_CR57","doi-asserted-by":"publisher","first-page":"4989","DOI":"10.4049\/jimmunol.1200068","volume":"189","author":"T Wu","year":"2012","unstructured":"Wu, T. et al. Smad3-deficient CD11b(+)Gr1(+) myeloid-derived suppressor cells prevent allograft rejection via the nitric oxide pathway. J. Immunol. 189, 4989\u20135000 (2012).","journal-title":"J. Immunol."},{"key":"BFncomms5696_CR58","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1002\/jcp.22891","volume":"227","author":"C Sun","year":"2012","unstructured":"Sun, C. et al. The phenotype and functional alterations of macrophages in mice with hyperglycemia for long term. J. Cell Physiol. 227, 1670\u20131679 (2012).","journal-title":"J. Cell Physiol."},{"key":"BFncomms5696_CR59","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.4049\/jimmunol.1300656","volume":"192","author":"B Sun","year":"2014","unstructured":"Sun, B. et al. Phosphatase Wip1 negatively regulates neutrophil migration and inflammation. J. Immunol. 192, 1184\u20131195 (2014).","journal-title":"J. Immunol."},{"key":"BFncomms5696_CR60","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1182\/blood-2012-05-432674","volume":"121","author":"G Liu","year":"2013","unstructured":"Liu, G. et al. Phosphatase Wip1 negatively regulates neutrophil development through p38 MAPK-STAT1. Blood 121, 519\u2013529 (2013).","journal-title":"Blood"},{"key":"BFncomms5696_CR61","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s11307-012-0596-5","volume":"15","author":"JS Gil","year":"2013","unstructured":"Gil, J. S. et al. Application of a rapid, simple, and accurate adenovirus-based method to compare PET reporter gene\/PET reporter probe systems. Mol. Imaging Biol. 15, 273\u2013281 (2013).","journal-title":"Mol. Imaging Biol."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms5696.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms5696","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms5696.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T22:10:06Z","timestamp":1672956606000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms5696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,1]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,12,17]]}},"alternative-id":["BFncomms5696"],"URL":"https:\/\/doi.org\/10.1038\/ncomms5696","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,1]]},"assertion":[{"value":"2 June 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2014","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2014","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4696"}}