Dendritic cell‐derived thrombospondin‐1 is critical for the generation of the ocular surface Th17 response to desiccating stress

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

关键词: TGF‐;    β;    IL‐;    17A;    IFN‐;    γ;    dry eye;    conjunctiva;    corneal permeability;    goblet cells;   

DOI  :  10.1189/jlb.1012524

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TSP‐1isaphysiologicactivatorofTGF‐β,acriticalinductionfactorforTh17‐mediatedimmunity.ThepurposeofthisstudywastoinvestigatetheroleofTSP‐1intheinductionoftheTh17ocularsurfaceresponsetoDS.TSP‐1KOandWTmiceweresubjectedtoDS5andDS10),andparametersofocularsurfacedisease,includingcornealbarrierfunction,conjunctivalCD4+Tcellinfiltration,andGCdensity,wereevaluated.TSP‐1KOmicesubjectedtoDShadlesscornealbarrierdisruption,reducedlossofPAS+GC,anddecreasedCD4+Tcellinfiltrationintheconjunctiva.IncontrasttoWT,TSP‐1KOmicefailedtoup‐regulateMMP‐3andMMP‐9mRNAtranscriptsinthecorneaandIL‐17AmRNAtranscriptsintheconjunctiva.RAG‐1KOrecipientsofadoptivelytransferredCD4+TcellsisolatedfromTSP‐1KOmicesubjectedtoDS5showedmilderdry‐eyephenotypeandlessconjunctivalinflammationthanrecipientsofCD4+TcellsfromDS5WTcontrol.ReconstitutionofTSP‐1KOmicewithWTDCspriortoDSreversedtheresistanceoftheTSP‐1KOtoDS‐inducedimmunopathology.Inconclusion,DC‐derivedTSP‐1iscriticalforgeneratingtheTh17ocularsurfaceresponsetoDS...

【 授权许可】

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