| Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
| Impaired T cell function in argininosuccinate synthetase deficiency | |
| 关键词: immunity; arginine; metabolism; differentiation; | |
| DOI : 10.1189/jlb.1AB0714-365R | |
| 学科分类：生理学 | |
| 来源: Federation of American Societies for Experimental Biology | |
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【 摘 要 】
ASS1isacytosolicenzymethatplaysaroleintheconversionofcitrullinetoarginine.Inhumanandmousetissues,ASS1proteinisfoundinseveralcomponentsoftheimmunesystem,includingthethymusandTcells.However,theroleofASS1inthesetissuesremainstobedefined.ConsiderableattentionhasbeenfocusedrecentlyontheroleofmetabolisminTcelldifferentiationandfunction.BasedontheexpressionofASS1intheimmunesystem,wehypothesizedthatASS1deficiencywouldresultinTcelldefects.Toevaluatethisquestion,wecharacterizedimmunefunctioninhypomorphicfold/foldmice.AnalysisofsplenicTcellsbyflowcytometryshowedamarkedreductioninTcellnumberswithnormalexpressionofactivationsurfacemarkers.GenetherapycorrectionofliverASS1toenhancesurvivalresultedinapartialrecoveryofsplenicTcellsforcharacterization.InvitroandinvivostudiesdemonstratedthepersistenceoftheASS1enzymedefectinTcellsandabnormalTcelldifferentiationandfunction.Overall,ourworksuggeststhatASS1playsaroleinTcellfunction,anddeficiencyproducesprimaryimmunedysfunction.Inaddition,thesedatasuggestthatpatientswithASS1deficiency(citrullinemiatypeI)mayhaveTcelldysfunction...
【 授权许可】
CC BY
【 预 览 】
| Files | Size | Format | View |
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| RO201904047120542ZK.pdf | 1223KB |  download |
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