Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Dendritic cell‐derived thrombospondin‐1 is critical for the generation of the ocular surface Th17 response to desiccating stress | |
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...
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