γδ T cells protect against LPS‐induced lung injury

[摘要] γδTlymphocytesareauniqueTcellpopulationwithimportantanti‐inflammatorycapabilities.Theirroleinacutelunginjury,however,ispoorlyunderstoodbutmayprovidesignificantinsightintolung‐protectivemechanismsoccurringafterinjury.Inamurinemodeloflunginjury,wild‐typeC57BL/6andTCRδ−/−micewereexposedtoEscherichiacoliLPS,followedbyanalysisofγδTcellandmacrophagesubsets.IntheabsenceofγδTcells,TCRδ−/−micedevelopedincreasedinflammationandalveolar‐capillaryleakcomparedwithwild‐typeC57BL/6miceafterLPSexposurethatcorrelatedwithexpansionofdistinctmacrophagepopulations.ClassicallyactivatedM1macrophageswereincreasedinthelungofTCRδ−/−miceatd1,4,and7afterLPSexposurethatpeakedatd4andpersistedatd7comparedwithwild‐typeanimals.InresponsetoLPS,Vγ1andVγ7γδTcellswereexpandedinthelungandexpressedIL‐4.CocultureexperimentsshoweddecreasedexpressionofTNF‐αbyresidentalveolarmacrophagesinthepresenceofγδTcellsthatwasreversedinthepresenceofananti‐IL‐4‐blockingantibody.TreatmentofmicewithrIL4resultedinreducednumbersofM1macrophages,inflammation,andalveolar‐capillaryleak.Therefore,onemechanismbywhichVγ1andVγ7γδTcellsprotectagainstLPS‐inducedlunginjuryisthroughIL‐4expression,whichdecreasesTNF‐αproductionbyresidentalveolarmacrophages,thusreducingaccumulationofM1macrophages,inflammation,andalveolar‐capillaryleak...

[学科分类] 生理学

[关键词] macrophages;IL‐4;ARDS;alveolar‐capillary leak;TNF‐α