{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:55:43Z","timestamp":1791172543033,"version":"4.1.0"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"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":[[2011,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The reduced efficiency of the mammalian immune system with aging increases host susceptibility to infectious and autoimmune diseases. However, the mechanisms responsible for these pathologic changes are not well understood. In this study, we demonstrate that the bone marrow, blood, and secondary lymphoid organs of healthy aged mice possess increased numbers of immature myeloid cells that are phenotypically similar to myeloid-derived suppressor cells found in lymphoid organs of mice with progressive tumors and other pathologic conditions associated with chronic inflammation. These cells are characterized by the presence of Gr1 and CD11b markers on their surfaces. Gr1+CD11b+ cells isolated from aged mice possess an ability to suppress T cell proliferation\/activation and produce heightened levels of proinflammatory cytokines, both constitutively and upon activation, including IL-12, which promotes an excessive production of IFN-\u03b3. IFN-\u03b3 priming is essential for excessive proinflammatory cytokine production and the suppressive activities by Gr1+CD11b+ cells from aged mice. These cells suppress T cell proliferation through an NO-dependent mechanism, as depletion of splenic Gr1+ cells reduces NO levels and restores T cell proliferation. Insights into mechanisms responsible for the proinflammatory and immune suppressive activities of Gr1+CD11b+ cells from aged mice have uncovered a defective PI3K\u2013Akt signaling pathway, leading to a reduced Akt-dependent inactivation of GSK3\u03b2. Our data demonstrate that abnormal activities of the Gr1+CD11b+ myeloid cell population from aged mice could play a significant role in the mechanisms responsible for immune senescence.<\/jats:p>","DOI":"10.4049\/jimmunol.1002987","type":"journal-article","created":{"date-parts":[[2010,12,10]],"date-time":"2010-12-10T22:58:45Z","timestamp":1292021925000},"page":"697-707","source":"Crossref","is-referenced-by-count":129,"title":["A Role for Immature Myeloid Cells in Immune Senescence"],"prefix":"10.1093","volume":"186","author":[{"given":"Elena Y","family":"Enioutina","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT 84132"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Bareyan","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT 84132"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond A","family":"Daynes","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT 84132"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,1,15]]},"reference":[{"key":"2025032410594840100_r1","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1189\/jlb.0809542","article-title":"Leukocyte function in the aging immune system","volume":"87","author":"Desai","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"2025032410594840100_r2","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.exger.2008.05.016","article-title":"Innate immunity and aging","volume":"43","author":"Gomez","year":"2008","journal-title":"Exp. Gerontol."},{"key":"2025032410594840100_r3","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.it.2009.03.012","article-title":"Aging and innate immunity in the mouse: impact of intrinsic and extrinsic factors","volume":"30","author":"Kovacs","year":"2009","journal-title":"Trends Immunol."},{"key":"2025032410594840100_r4","doi-asserted-by":"crossref","first-page":"S116","DOI":"10.1016\/j.jcpa.2009.10.002","article-title":"Fading immune protection in old age: vaccination in the elderly","volume":"142","author":"Grubeck-Loebenstein","year":"2010","journal-title":"J. Comp. Pathol."},{"key":"2025032410594840100_r5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1556\/AMicr.56.2009.3.1","article-title":"Immunosenescence and vaccination of the elderly, I. Age-related immune impairment","volume":"56","author":"Ongr\u00e1di","year":"2009","journal-title":"Acta Microbiol. Immunol. Hung."},{"key":"2025032410594840100_r6","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1089\/152308603770310185","article-title":"Role of redox imbalance in the molecular mechanisms responsible for immunosenescence","volume":"5","author":"Daynes","year":"2003","journal-title":"Antioxid. Redox Signal."},{"key":"2025032410594840100_r7","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.2174\/138161209789058110","article-title":"An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging","volume":"15","author":"De la Fuente","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"2025032410594840100_r8","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.mad.2006.01.008","article-title":"Oxidative damage and age-related functional declines","volume":"127","author":"Martin","year":"2006","journal-title":"Mech. Ageing Dev."},{"key":"2025032410594840100_r9","doi-asserted-by":"crossref","first-page":"32833","DOI":"10.1074\/jbc.273.49.32833","article-title":"Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor-kappaB signaling, and reduces inflammatory cytokine production in aging","volume":"273","author":"Poynter","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2025032410594840100_r10","doi-asserted-by":"crossref","first-page":"453892","DOI":"10.1155\/2010\/453892","article-title":"Role of reactive oxygen species in the progression of type 2 diabetes and atherosclerosis","volume":"2010","author":"Kaneto","year":"2010","journal-title":"Mediators Inflamm."},{"key":"2025032410594840100_r11","first-page":"689","article-title":"Is there a role of free oxygen radicals in primary male osteoporosis?","volume":"23","author":"Yalin","year":"2005","journal-title":"Clin. Exp. Rheumatol."},{"key":"2025032410594840100_r12","doi-asserted-by":"crossref","first-page":"5191","DOI":"10.1128\/IAI.00759-08","article-title":"Conditions that diminish myeloid-derived suppressor cell activities stimulate cross-protective immunity","volume":"76","author":"Heithoff","year":"2008","journal-title":"Infect. Immun."},{"key":"2025032410594840100_r13","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.4049\/jimmunol.146.8.2737","article-title":"Immunosuppression induced by attenuated Salmonella. Evidence for mediation by macrophage precursors","volume":"146","author":"al-Ramadi","year":"1991","journal-title":"J. Immunol."},{"key":"2025032410594840100_r14","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1002\/eji.1830220911","article-title":"Immunosuppression induced by nitric oxide and its inhibition by interleukin-4","volume":"22","author":"al-Ramadi","year":"1992","journal-title":"Eur. J. Immunol."},{"key":"2025032410594840100_r15","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/nri2506","article-title":"Myeloid-derived suppressor cells as regulators of the immune system","volume":"9","author":"Gabrilovich","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"2025032410594840100_r16","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.canlet.2008.03.012","article-title":"Myeloid-derived suppressor cell role in tumor-related inflammation","volume":"267","author":"Dolcetti","year":"2008","journal-title":"Cancer Lett."},{"key":"2025032410594840100_r17","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00430-010-0151-4","article-title":"Subsets, expansion and activation of myeloid-derived suppressor cells","volume":"199","author":"Ribechini","year":"2010","journal-title":"Med. Microbiol. Immunol. (Berl.)"},{"key":"2025032410594840100_r18","doi-asserted-by":"crossref","first-page":"4499","DOI":"10.4049\/jimmunol.0802740","article-title":"Myeloid-derived suppressor cells: linking inflammation and cancer","volume":"182","author":"Ostrand-Rosenberg","year":"2009","journal-title":"J. Immunol."},{"key":"2025032410594840100_r19","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1158\/0008-5472.CAN-06-3037","article-title":"The terminology issue for myeloid-derived suppressor cells","volume":"67","author":"Gabrilovich","year":"2007","journal-title":"Cancer Res."},{"key":"2025032410594840100_r20","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/nri1668","article-title":"Regulation of immune responses by L-arginine metabolism","volume":"5","author":"Bronte","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"2025032410594840100_r21","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1084\/jem.174.6.1323","article-title":"Platelet-derived growth factor is a potent biologic response modifier of T cells","volume":"174","author":"Daynes","year":"1991","journal-title":"J. Exp. Med."},{"key":"2025032410594840100_r22","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1093\/intimm\/9.5.745","article-title":"IL-12 directly stimulates expression of IL-10 by CD5+ B cells and IL-6 by both CD5+ and CD5- B cells: possible involvement in age-associated cytokine dysregulation","volume":"9","author":"Spencer","year":"1997","journal-title":"Int. Immunol."},{"key":"2025032410594840100_r23","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1002\/eji.1830250436","article-title":"Reciprocal regulation of the nitric oxide synthase\/arginase balance in mouse bone marrow-derived macrophages by TH1 and TH2 cytokines","volume":"25","author":"Modolell","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"2025032410594840100_r24","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1016\/S0264-410X(00)00008-6","article-title":"Enhancement of common mucosal immunity in aged mice following their supplementation with various antioxidants","volume":"18","author":"Enioutina","year":"2000","journal-title":"Vaccine"},{"key":"2025032410594840100_r25","doi-asserted-by":"crossref","first-page":"4296","DOI":"10.4049\/jimmunol.0804344","article-title":"TLR-induced local metabolism of vitamin D3 plays an important role in the diversification of adaptive immune responses","volume":"182","author":"Enioutina","year":"2009","journal-title":"J. Immunol."},{"key":"2025032410594840100_r26","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.4049\/jimmunol.178.4.2517","article-title":"Glucocorticoid conditioning of myeloid progenitors enhances TLR4 signaling via negative regulation of the phosphatidylinositol 3-kinase-Akt pathway","volume":"178","author":"Zhang","year":"2007","journal-title":"J. Immunol."},{"key":"2025032410594840100_r27","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1084\/jem.20062602","article-title":"MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis","volume":"204","author":"Delano","year":"2007","journal-title":"J. Exp. Med."},{"key":"2025032410594840100_r28","doi-asserted-by":"crossref","first-page":"5791","DOI":"10.4049\/jimmunol.181.8.5791","article-title":"Subsets of myeloid-derived suppressor cells in tumor-bearing mice","volume":"181","author":"Youn","year":"2008","journal-title":"J. Immunol."},{"key":"2025032410594840100_r29","first-page":"218","article-title":"Inflammaging (inflammation + aging): a driving force for human aging based on an evolutionarily antagonistic pleiotropy theory?","volume":"2","author":"Goto","year":"2008","journal-title":"Biosci. Trends"},{"key":"2025032410594840100_r30","doi-asserted-by":"crossref","first-page":"5219","DOI":"10.4049\/jimmunol.150.12.5219","article-title":"Altered regulation of IL-6 production with normal aging. Possible linkage to the age-associated decline in dehydroepiandrosterone and its sulfated derivative","volume":"150","author":"Daynes","year":"1993","journal-title":"J. Immunol."},{"key":"2025032410594840100_r31","first-page":"395","article-title":"The \u2018Jaykay\u2019 stoma flange cutter","volume":"74","author":"Parker","year":"1992","journal-title":"Ann. R. Coll. Surg. Engl."},{"key":"2025032410594840100_r32","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1097\/00002371-199210000-00006","article-title":"Natural regulators of T-cell lymphokine production in vivo","volume":"12","author":"Daynes","year":"1992","journal-title":"J. Immunother."},{"key":"2025032410594840100_r33","doi-asserted-by":"crossref","first-page":"40","DOI":"10.2174\/187152809787582507","article-title":"The IL-12 family of cytokines in infection, inflammation and autoimmune disorders","volume":"8","author":"Gee","year":"2009","journal-title":"Inflamm. Allergy Drug Targets"},{"key":"2025032410594840100_r34","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/stem.5530120203","article-title":"Interleukin 12: a key modulator of immune function","volume":"12","author":"Wolf","year":"1994","journal-title":"Stem Cells"},{"key":"2025032410594840100_r35","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1079\/PNS2002173","article-title":"A role for the peroxisome proliferator-activated receptor alpha in T-cell physiology and ageing immunobiology","volume":"61","author":"Jones","year":"2002","journal-title":"Proc. Nutr. Soc."},{"key":"2025032410594840100_r36","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s00262-002-0280-8","article-title":"Immature myeloid cells and cancer-associated immune suppression","volume":"51","author":"Kusmartsev","year":"2002","journal-title":"Cancer Immunol. Immunother."},{"key":"2025032410594840100_r37","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.semcancer.2005.07.005","article-title":"Myeloid suppressor cells in cancer: recruitment, phenotype, properties, and mechanisms of immune suppression","volume":"16","author":"Serafini","year":"2006","journal-title":"Semin. Cancer Biol."},{"issue":"6","key":"2025032410594840100_r38","doi-asserted-by":"crossref","first-page":"1681S","DOI":"10.1093\/jn\/137.6.1681S","article-title":"Arginine and immunity","volume":"137","author":"Popovic","year":"2007","journal-title":"J. Nutr."},{"key":"2025032410594840100_r39","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.imbio.2006.03.004","article-title":"Age-dependent loss of na\u00efve T cells in TCR transgenic bone marrow chimeras","volume":"211","author":"Coleman","year":"2006","journal-title":"Immunobiology"},{"key":"2025032410594840100_r40","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.mad.2003.10.004","article-title":"Antigen-specific CD4 T cell clonal expansion and differentiation in the aged lymphoid microenvironment. I. The primary T cell response is unaffected","volume":"125","author":"Mittler","year":"2004","journal-title":"Mech. Ageing Dev."},{"key":"2025032410594840100_r41","doi-asserted-by":"crossref","first-page":"e631","DOI":"10.1371\/journal.pone.0000631","article-title":"Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection","volume":"2","author":"Barquero-Calvo","year":"2007","journal-title":"PLoS ONE"},{"key":"2025032410594840100_r42","doi-asserted-by":"crossref","first-page":"6912","DOI":"10.4049\/jimmunol.178.11.6912","article-title":"Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway","volume":"178","author":"Agrawal","year":"2007","journal-title":"J. Immunol."},{"key":"2025032410594840100_r43","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.it.2009.09.007","article-title":"Innate and adaptive immune responses regulated by glycogen synthase kinase-3 (GSK3)","volume":"31","author":"Beurel","year":"2010","journal-title":"Trends Immunol."},{"key":"2025032410594840100_r44","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s11064-006-9128-5","article-title":"Glycogen synthase kinase-3 (GSK3): inflammation, diseases, and therapeutics","volume":"32","author":"Jope","year":"2007","journal-title":"Neurochem. Res."},{"key":"2025032410594840100_r45","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1111\/j.1476-5381.2008.00085.x","article-title":"Glycogen synthase kinase 3: more than a namesake","volume":"156","author":"Rayasam","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"2025032410594840100_r46","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/ni1221","article-title":"Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3","volume":"6","author":"Martin","year":"2005","journal-title":"Nat. Immunol."},{"key":"2025032410594840100_r47","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.immuni.2006.02.014","article-title":"IFN-gamma suppresses IL-10 production and synergizes with TLR2 by regulating GSK3 and CREB\/AP-1 proteins","volume":"24","author":"Hu","year":"2006","journal-title":"Immunity"},{"key":"2025032410594840100_r48","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1055\/s-0028-1088302","article-title":"Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals","volume":"74","author":"Surh","year":"2008","journal-title":"Planta Med."},{"key":"2025032410594840100_r49","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/S1357-2725(99)00072-2","article-title":"SHIPs ahoy","volume":"31","author":"Krystal","year":"1999","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2025032410594840100_r50","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1073\/pnas.93.4.1689","article-title":"The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-triphosphate 5-phosphatase","volume":"93","author":"Damen","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032410594840100_r51","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.coi.2009.06.002","article-title":"Rejuvenation of the aging T cell compartment","volume":"21","author":"Holland","year":"2009","journal-title":"Curr. Opin. Immunol."},{"key":"2025032410594840100_r52","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.it.2009.04.007","article-title":"T-cell immunosenescence: lessons learned from mouse models of aging","volume":"30","author":"Maue","year":"2009","journal-title":"Trends Immunol."},{"key":"2025032410594840100_r53","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1023\/A:1020151401826","article-title":"Age-related changes in type 1 and type 2 cytokine production in humans","volume":"3","author":"Gardner","year":"2002","journal-title":"Biogerontology"},{"key":"2025032410594840100_r54","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.coi.2009.05.009","article-title":"Effects of aging on T cell function","volume":"21","author":"Haynes","year":"2009","journal-title":"Curr. Opin. Immunol."},{"key":"2025032410594840100_r55","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1474-9726.2009.00534.x","article-title":"Age-related alterations of gene expression patterns in human CD8+ T cells","volume":"9","author":"Cao","year":"2010","journal-title":"Aging Cell"},{"key":"2025032410594840100_r56","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.cellsig.2005.08.016","article-title":"Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging","volume":"18","author":"Larbi","year":"2006","journal-title":"Cell. Signal."},{"key":"2025032410594840100_r57","doi-asserted-by":"crossref","first-page":"11021","DOI":"10.1158\/0008-5472.CAN-07-2593","article-title":"Mechanism of all-trans retinoic acid effect on tumor-associated myeloid-derived suppressor cells","volume":"67","author":"Nefedova","year":"2007","journal-title":"Cancer Res."},{"key":"2025032410594840100_r58","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1093\/intimm\/9.10.1581","article-title":"Constitutive activation of NF-kappa B in an animal model of aging","volume":"9","author":"Spencer","year":"1997","journal-title":"Int. Immunol."},{"key":"2025032410594840100_r59","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1006\/cimm.1999.1525","article-title":"Age-associated alterations in splenic iNOS regulation: influence of constitutively expressed IFN-gamma and correction following supplementation with PPARalpha activators or vitamin E","volume":"195","author":"Poynter","year":"1999","journal-title":"Cell. Immunol."},{"key":"2025032410594840100_r60","doi-asserted-by":"crossref","first-page":"4880","DOI":"10.4049\/jimmunol.174.8.4880","article-title":"STAT1 signaling regulates tumor-associated macrophage-mediated T cell deletion","volume":"174","author":"Kusmartsev","year":"2005","journal-title":"J. Immunol."},{"key":"2025032410594840100_r61","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.humimm.2009.02.008","article-title":"Tumor-associated macrophages and the related myeloid-derived suppressor cells as a paradigm of the diversity of macrophage activation","volume":"70","author":"Mantovani","year":"2009","journal-title":"Hum. Immunol."},{"key":"2025032410594840100_r62","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nri978","article-title":"Alternative activation of macrophages","volume":"3","author":"Gordon","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2025032410594840100_r63","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/S0531-5565(99)00065-0","article-title":"Phenotypic and functional characteristics of circulating monocytes of elderly persons","volume":"34","author":"Sadeghi","year":"1999","journal-title":"Exp. Gerontol."},{"key":"2025032410594840100_r64","doi-asserted-by":"crossref","first-page":"S504","DOI":"10.1086\/432007","article-title":"The immunopathogenesis of sepsis in elderly patients","volume":"41","author":"Opal","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"2025032410594840100_r65","doi-asserted-by":"crossref","first-page":"4666","DOI":"10.4049\/jimmunol.181.7.4666","article-title":"Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells","volume":"181","author":"Sinha","year":"2008","journal-title":"J. Immunol."},{"key":"2025032410594840100_r66","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1084\/jem.20080132","article-title":"Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein","volume":"205","author":"Cheng","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025032410594840100_r67","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1016\/j.bcp.2006.05.017","article-title":"S100A8 and S100A9 in inflammation and cancer","volume":"72","author":"Gebhardt","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"2025032410594840100_r68","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00403-009-0960-8","article-title":"Changes in S100A8 expression in UV-irradiated and aged human skin in vivo","volume":"301","author":"Lee","year":"2009","journal-title":"Arch. Dermatol. Res."},{"key":"2025032410594840100_r69","doi-asserted-by":"crossref","first-page":"e5562","DOI":"10.1371\/journal.pone.0005562","article-title":"Amyloid formation by the pro-inflammatory S100A8\/A9 proteins in the ageing prostate","volume":"4","author":"Yanamandra","year":"2009","journal-title":"PLoS ONE"},{"key":"2025032410594840100_r70","article-title":"Inflammation-associated S100 proteins: new mechanisms that regulate function","author":"Goyette","year":"2010","journal-title":"Amino Acids"},{"key":"2025032410594840100_r71","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1007\/s00125-009-1458-9","article-title":"Multiple levels of regulation determine the role of the receptor for AGE (RAGE) as common soil in inflammation, immune responses and diabetes mellitus and its complications","volume":"52","author":"Bierhaus","year":"2009","journal-title":"Diabetologia"},{"key":"2025032410594840100_r72","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1139\/Y09-054","article-title":"S100A8\/A9: a mediator of severe asthma pathogenesis and morbidity?","volume":"87","author":"Halayko","year":"2009","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"2025032410594840100_r73","doi-asserted-by":"crossref","first-page":"689","DOI":"10.4049\/jimmunol.168.2.689","article-title":"Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism","volume":"168","author":"Mazzoni","year":"2002","journal-title":"J. Immunol."},{"key":"2025032410594840100_r74","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.mad.2007.10.003","article-title":"Age-related increase of tumor susceptibility is associated with myeloid-derived suppressor cell mediated suppression of T cell cytotoxicity in recombinant inbred BXD12 mice","volume":"128","author":"Grizzle","year":"2007","journal-title":"Mech. Ageing Dev."},{"key":"2025032410594840100_r75","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0065-230X(05)94002-5","article-title":"Activation of AKT kinases in cancer: implications for therapeutic targeting","volume":"94","author":"Bellacosa","year":"2005","journal-title":"Adv. Cancer Res."},{"key":"2025032410594840100_r76","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1016\/j.bcp.2010.07.014","article-title":"Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential","volume":"80","author":"Paine","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"2025032410594840100_r77","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3904\/kjim.2010.25.2.119","article-title":"Molecular mechanism of insulin resistance in obesity and type 2 diabetes","volume":"25","author":"Choi","year":"2010","journal-title":"Korean J. Intern. Med."},{"key":"2025032410594840100_r78","first-page":"19","article-title":"Physiological regulation of Akt activity and stability","volume":"2","author":"Liao","year":"2010","journal-title":"Am J Transl Res"},{"key":"2025032410594840100_r79","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1749-6632.2009.05134.x","article-title":"Phosphoinositide 3-kinase and the mammalian target of rapamycin pathways control T cell migration","volume":"1183","author":"Finlay","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2025032410594840100_r80","doi-asserted-by":"crossref","first-page":"34","DOI":"10.2174\/138161210789941865","article-title":"The PKB\/AKT pathway in cancer","volume":"16","author":"Carnero","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"2025032410594840100_r81","doi-asserted-by":"crossref","first-page":"8777","DOI":"10.4049\/jimmunol.177.12.8777","article-title":"SHIP1 negatively regulates proliferation of osteoclast precursors via Akt-dependent alterations in D-type cyclins and p27","volume":"177","author":"Zhou","year":"2006","journal-title":"J. Immunol."},{"key":"2025032410594840100_r82","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0065-230X(09)02002-8","article-title":"PI3K\/PTEN signaling in angiogenesis and tumorigenesis","volume":"102","author":"Jiang","year":"2009","journal-title":"Adv. Cancer Res."},{"key":"2025032410594840100_r83","doi-asserted-by":"crossref","first-page":"6325","DOI":"10.4049\/jimmunol.179.9.6325","article-title":"Macrophages from 11beta-hydroxysteroid dehydrogenase type 1-deficient mice exhibit an increased sensitivity to lipopolysaccharide stimulation due to TGF-beta-mediated up-regulation of SHIP1 expression","volume":"179","author":"Zhang","year":"2007","journal-title":"J. Immunol."},{"key":"2025032410594840100_r84","doi-asserted-by":"crossref","first-page":"856","DOI":"10.4049\/jimmunol.0804033","article-title":"Glycogen synthase kinase-3beta facilitates IFN-gamma-induced STAT1 activation by regulating Src homology-2 domain-containing phosphatase 2","volume":"183","author":"Tsai","year":"2009","journal-title":"J. Immunol."},{"key":"2025032410594840100_r85","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1002\/jcb.21868","article-title":"IFN-gamma synergizes with LPS to induce nitric oxide biosynthesis through glycogen synthase kinase-3-inhibited IL-10","volume":"105","author":"Lin","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"2025032410594840100_r86","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1196\/annals.1395.008","article-title":"Do membrane rafts contribute to human immunosenescence?","volume":"1100","author":"Tomoiu","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2025032410594840100_r87","doi-asserted-by":"crossref","first-page":"32385","DOI":"10.1074\/jbc.M604878200","article-title":"TcR and TcR-CD28 engagement of protein kinase B (PKB\/AKT) and glycogen synthase kinase-3 (GSK-3) operates independently of guanine nucleotide exchange factor VAV-1","volume":"281","author":"Wood","year":"2006","journal-title":"J. Biol. Chem."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/186\/2\/697\/61614426\/1002987.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/186\/2\/697\/61614426\/1002987.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T04:27:31Z","timestamp":1743136051000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/186\/2\/697\/7978046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1]]},"references-count":87,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2011,1,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1002987","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.11816956.12922054","asserted-by":"object"}]},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,1]]},"published":{"date-parts":[[2011,1]]}}}