Dynamics of Intraocular IFN-γ, IL-17 and IL-10-Producing Cell Populations during Relapsing and Monophasic Rat Experimental Autoimmune Uveitis 英文参考文献.docVIP

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2017-05-11 发布于上海
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Dynamics of Intraocular IFN-γ, IL-17 and IL-10-Producing Cell Populations during Relapsing and Monophasic Rat Experimental Autoimmune Uveitis 英文参考文献.doc

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Dynamics of Intraocular IFN-γ, IL-17 and IL-10-Producing Cell Populations during Relapsing and Monophasic Rat Experimental Autoimmune Uveitis 英文参考文献

DynamicsofIntraocularIFN-c,IL-17andIL-10-Producing CellPopulationsduringRelapsingandMonophasicRat ExperimentalAutoimmuneUveitis UlrikeKaufmann,MariaDiedrichs-Mo¨hring,GerhildWildner* SectionofImmunobiology,Dept.ofOphthalmology,KlinikumderUniversita¨t, Munich,Germany Abstract Amajorlimitationofmostanimalmodelsofautoimmunediseasesisthattheydonotreproducethechronicorrelapsing- remittingpatterncharacteristicofmanyhumanautoimmunediseases.Thisproblemhasbeenovercomeinourratmodels ofexperimentally induced monophasic orrelapsing-remitting autoimmuneuveitis (EAU), whichdepend on theinducing antigenpeptidesfromretinalS-Antigen(monophasicEAU)orinterphotoreceptorretinoid-bindingprotein(relapsingEAU). ThesemodelsenableustocompareautoreactiveandregulatoryTcellpopulations.Intraocular,butnotperipheralTcells differ in their cytokine profiles (IFN-c, IL-17 and IL-10) at distinct time points during monophasic or relapsing EAU. Only intraocular T cells concomitantly produced IFN-c, IL-17 and/or IL-10. Monophasic EAU presented rising numbers of cells expressingIFN-candIL-17(Th1/Th17)andcellsexpressingIL-10orFoxp3.Duringrelapsinguveitisanincreaseofintraocular IFN-c+cellsandaconcomitantdecreaseofIL-17+cells wasdetected,while IL-10+populationsremainedstable.Foxp3+ cellsandcellsexpressingIL-10,evenincombinationwithIFN-corIL-17,increasedduringtheresolutionofmonophasicEAU, suggestingaregulatoryrolefortheseTcells.Ingeneral,cellsproducingmultiplecytokinesincreasedinmonophasicand decreased in relapsing EAU. The distinct appearance of certain intraocular populations with characteristics of regulatory cellspointstoadifferentialinfluenceoftheocularenvironmentonTcellsthatinduceacuteandmonophasicorrelapsing disease. Here we provide evidence that different autoantigens can elicit distinct and differently regulated immune responses. IFN-c, but not IL-17 seems to be the key player in relapsing-remitting uveitis, as shown by increased, synchronized relapses after intraocular application of IFN-c.