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| 1 | Critical role of OX40 signaling in the TCR-independent phase of human and murine thymic Treg generation显示文摘Regulatory T cells(Tregs)play a pivotal role in immune-tolerance,and loss of Treg function can lead to the development of autoimmunity.Natural Tregs generated in the thymus substantially contribute to the Treg pool in the periphery,where they suppress self-reactive effector T cells(Teff)responses.Recently,we showed that OX40L(TNFSF4)is able to drive selective proliferation of peripheral Tregs independent of canonical antigen presentation(CAP-independent)in the presence of low-dose IL-2.Therefore,we hypothesized that OX40 signaling might be integral to the TCR-independent phase of murine and human thymic Treg(tTreg)development.Development of tTregs is a two-step process:Strong T-cell receptor(TCR)signals in combination with co-signals from the TNFRSF members facilitate tTreg precursor selection,followed by a TCR-independent phase of tTreg development in which their maturation is driven by IL-2.Therefore,we investigated whether OX40 signaling could also play a critical role in the TCR-independent phase of tTreg development.OX40−/−mice had significantly reduced numbers of CD25−Foxp3low tTreg precursors and CD25+Foxp3+mature tTregs,while OX40L treatment of WT mice induced significant proliferation of these cell subsets.Relative to tTeff cells,OX40 was expressed at higher levels in both murine and human tTreg precursors and mature tTregs.In ex vivo cultures,OX40L increased tTreg maturation and induced CAP-independent proliferation of both murine and human tTregs,which was mediated through the activation of AKT-mTOR signaling.These novel findings show an evolutionarily conserved role for OX40 signaling in tTreg development and proliferation,and might enable the development of novel strategies to increase Tregs and suppress autoimmunity. | Prabhakaran Kumar Alejandra Marinelarena Divya Raghunathan Vandhana K Ragothaman Shikha Saini Palash Bhattacharya Jilao Fan Alan L Epstein Ajay V Maker Bellur S Prabhakar | 2019 | Cellular & Molecular Immunology2019，16，2： | 4 |
| 2 | MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B 显示文摘 | Gosling J lay maker S Gu L | 1999 | J Clin Invest1999，103，6： | 1 |
| 3 | Cyst fluid biomarkers for intraductal papillary mutinous neoplasms of the pancreas: A critical review from the international expert meet- ing on pancreatic branch-duct-intraductal papillary mucinous neoplasms显示文摘 | MAKER A V CARRARA S JAMIESON N B | 2015 | Journal of the American College of Surgeons2015，220，2： | 1 |
| 4 | A comparative study of trimethylamine-N-oxide biosynthesis 显示文摘 | MAKER J R STRUEMPLER A CHAYKIN S | 1963 | Biochimica et Biophysica Acta1963，71，： | 1 |
| 5 | Wharton on managing emerging technologies 显示文摘 | Pau J H George S D maker S | 1982 | Journal of Economic1982，20，2： | 1 |
| 6 | Finite elementimplementation of incompressible, transversely isotropichyperelasticity 显示文摘 | Weiss J A Maker B N Govindjee S | 1996 | Computer Methods in AppliedMechanics and Engineering1996，135，1： | 1 |
| 7 | Couple of dopamine oxidation monoamine oxidation via the generation of hydrogen peroxide in rat brain homogenates显示文摘 | Maker H S Weiss C Silides D J | 1981 | Neurochem1981，36，2： | 1 |
| 8 | Internet-based mobile Ad Hoc networking显示文摘 | Corson M S Maker J P Cirincione G H | 1999 | IEEE Internet Computing1999，3，4： | 1 |
| 9 | The activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase in rat tissues显示文摘 | Weissbarth S Maker HS Raes I | | 0，，： | 1 |
| 10 | Start-up of moving bed biofilm reactors for deammonification:the role of hydraulic retention time,alkalinity and oxygen supply显示文摘 | Gaul T Maker S Kunst S | 2005 | Water Science and Technology2005，52，7： | 1 |
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