EphB2‐mediated interactions are essential for proper migration of T cell progenitors during fetal thymus colonization

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: hematopoietic precursors;    thymocytes;    Eph receptors;    ephrins;   

DOI  :  10.1189/jlb.0210079

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Theephrin‐Ephligandreceptorpairisknowntocontroltherepulsion/adhesionprocessindifferenttissues,includingtheimmunesystem.Herein,weevaluatedtheroleofEphB2receptorsinTcellprogenitormigrationduringinvitrothymuscolonizationandtoECMorchemokinestimuli.EphB2andtheirligands,ephrin‐B1andephrin‐B2,areexpressedinBM‐derivedprogenitors,andEphB2−/−cellshaddiminishedthymuscolonizationcapacity.Conversely,EphB2LacZcells,whichmaintainapreservedephrin‐bindingdomain,werecapableofcolonizingWTthymusessimilarlytoWTprogenitors,highlightingtheimportanceofreversesignalstransmittedtonormalfetalthymus.However,theEphB2receptorexpressedbymicroenvironmentalcellsalsodrivesprogenitorimmigration,asrecolonizationofEphB2‐deficientfetalthymuseswascompromisedprofoundly.Additionally,weobservedlowerdepositionsofECMandchemokinesonEphB2‐deficientthymusesbutnochangesintheirreceptorexpressiononBM‐derivedprogenitorsanddevelopingthymocytes.MigrationofEphB2‐deficientprogenitorsandthymocyteswasalsoreducedthroughECMorchemokinestimuli.Furthermore,ephrin‐B1costimulationalsoinhibitedhaptotaxisandchemotaxisofWTbutnotEphB2LacZcells,demonstratingthespecificinvolvementofEphB2signalingonTcellprogenitormigration.OurdatasuggesttherelevanceofanonactivatedEphB2forregulatingTcellprogenitormigrationanditsmodulationuponephrin‐Bengagement...

【 授权许可】

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