1,25-Dihydroxyvitamin D3 Inhibits the Differentiation and Migration of TH17 Cells to Protect against Experimental Autoimmune Encephalomyelitis 英文参考文献.docVIP

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1,25-Dihydroxyvitamin D3 Inhibits the Differentiation and Migration of TH17 Cells to Protect against Experimental Autoimmune Encephalomyelitis 英文参考文献.doc

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1,25-Dihydroxyvitamin D3 Inhibits the Differentiation and Migration of TH17 Cells to Protect against Experimental Autoimmune Encephalomyelitis 英文参考文献

1,25-DihydroxyvitaminD3InhibitstheDifferentiation andMigrationofTH17CellstoProtectagainst ExperimentalAutoimmuneEncephalomyelitis Jae-HoonChang1,Hye-RanCha1,Dong-SupLee2,KyoungYulSeo1,3,Mi-NaKweon1* 1MucosalImmunologySection,LaboratoryScienceDivision,InternationalVaccineInstitute,Seoul,Korea,2CancerResearchInstitute,SeoulNationalUniversityCollegeof Medicine,Seoul,Korea,3DepartmentofOphthalmology,InstituteforVisionResearch,YonseiUniversityCollegeofMedicine,Seoul,Korea Abstract Background:VitaminD3,themostphysiologicallyrelevantformofvitaminD,isanessentialorganiccompoundthathas been shown to have a crucial effect on the immune responses. Vitamin D3 ameliorates the onset of the experimental autoimmuneencephalomyelitis(EAE);however,thedirecteffectofvitaminD3onTcellsislargelyunknown. Methodology/Principal Findings: In an in vitro system using cells from mice, the active form of vitamin D3 (1,25- dihydroxyvitaminD3)suppressesbothinterleukin(IL)-17-producingTcells(TH17)andregulatoryTcells(Treg)differentiation viaavitaminDreceptorsignal.Theabilityof1,25-dihydroxyvitaminD3(1,25(OH)2D3)toreducetheamountofIL-2regulates the generation of Treg cells, but not TH17 cells. Under TH17-polarizing conditions, 1,25(OH)2D3 helps to increase the numbers of IL-10-producing T cells, but 1,25(OH)2D3’s negative regulation of TH17 development is still defined in the IL-102/2Tcells.AlthoughtheSTAT1signalreciprocallyaffectsthesecretionofIL-10andIL-17,1,25(OH)2D3inhibitsIL-17 production in STAT12/2 T cells. Most interestingly, 1,25(OH)2D3 negatively regulates CCR6 expression which might be essentialforTH17cellstoenterthecentralnervoussystemandinitiateEAE. Conclusions/Significance: Our present results in an experimental murine model suggest that 1,25(OH)2D3 can directly regulateTcelldifferentiationandcouldbeappliedinpreventiveandtherapeuticstrategiesforTH17-mediatedautoimmune diseases. Citation:ChangJ-H,ChaH-R,LeeD-S,SeoKY,KweonM-N(2010)1,25-DihydroxyvitaminD3InhibitstheDifferentiationandMigrat