Human adenosine deaminase 2 induces differentiation of monocytes into macrophages and stimulates proliferation of T helper cells and macrophages

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

关键词: innate immunity;    adaptive immunity;    development;   

DOI  :  10.1189/jlb.1109764

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ADAsplayapivotalroleinregulatingthelevelofadenosine,asignalingmoleculecontrollingavarietyofcellularresponsesbybindingtoandactivatingfourADRs.Twoenzymes,ADA1andADA2,areknowntopossessADAactivityinhumans.AlthoughthestructureofADA1anditsroleinlymphocyticactivationhavebeenknownforalongtime,thestructureandfunctionofADA2,amemberofADGF,remainenigmatic.Here,wefoundthatADA2issecretedbymonocytesundergoingdifferentiationintomacrophagesorDCsandthatitbindstothecellsurfaceviaproteoglycansandADRs.WedemonstratethatADA1andADA2increasetherateofproliferationofmonocyte‐activatedCD4+Tcellsindependentlyoftheircatalyticactivity.WealsoshowthatADA2inducesTcell‐dependentdifferentiationofmonocytesintomacrophagesandstimulatesmacrophageproliferation.Ourdiscoveryofthegrowthfactor‐likeactivityofADA2explainsclinicalobservationsandsuggeststhatthisenzymecouldbeusedasadrugcandidatetomodulatetheimmuneresponsesduringinflammationandcancer...

【 授权许可】

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