Hypomorphic mutation in the RAG2 gene affects dendritic cell distribution and migration

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

关键词: Omenn syndrome;    primary immunodeficiency;    immune dysregulation;   

DOI  :  10.1189/jlb.0713365

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

OSisaseverecombinedimmunodeficiencycharacterizedbyerythrodermiaandprotracteddiarrheaasaresultofinfiltrationofoligoclonal‐activatedTcells,causedbyhypomorphicmutationsinRAGs.TheRAG2R229QmousemodelfullyrecapitulatestheclinicalOSphenotype.WeevaluatedwhetherTandBcelldefects,togetherwiththeabnormallymphoidstructure,couldaffectDChomeostasisandfunction.HighdensityofLCswasobservedinskinbiopsiesofOmennpatientsandinthedermaofRAG2R229Qmice,correlatingwiththepresenceoferythrodermia.InvivomodelsofcutaneousskinpaintingandCHSdemonstratedadecreasedmigrationofRAG2R229QDCs—inparticular,LCs—intodrainingLNs.Interestingly,atsteadystate,RAG2R229QmiceshowedareductioninDCnumberinallhematopoieticorgansexceptLNs.AnalysisoftheMHCIImarkerrevealedadiminishedexpressionalsoupontheLPS‐driveninflammatorycondition.DespitethedecreasednumberofperipheralDCs,BMpre‐cDCswerepresentinnormalnumbercomparedwithRAG2+/+controls,whereaspDCsandmonocyteswerereducedsignificantly.Overall,theseresultspointtoasecondarydefectintheDCcompartment,whichcontributestoclinicalmanifestationsandautoimmunityinOS...

【 授权许可】

CC BY