PaperReading
01
CDSignalingRegulatesAcuteColitisviaRALDH2-ExpressingCD11bCD+DCs
CellReports
Weknow,CD,apotentcostimulatoryreceptorforCD8+Tcells,isexpressedinvariousnon-Tcells,butlittleisknownaboutitsregulatoryfunctionsinthesecells.Inthisstudy,theauthorsshowthatCDsignaling,specificallyinintestinalCD11bCD+dendriticcells(DCs),restrictsacutecolitisprogression.Mechanistically,CDengagementactivatesTAK1andsubsequentlystimulatestheAMPK-PGC-1aaxistoenhanceexpressionoftheAldh1a2geneencodingtheretinoicacid(RA)metabolizingenzymeRALDH2.RAcanactonCD11b+CDDCsandinduceSOCS3expression,which,inturn,suppressesp38MAPKactivationandinterleukin-23(IL-23)production.AdministrationofRAinDC-specificCD/micerepressesIL-23-producingCD11b+CDDCsandTH17cells,indicatingthatRAisamajorinhibitoryeffectormoleculeagainstintestinalCD11b+CDDCs.Additionally,thetherapeuticeffectoftheanti-CDantibodyisabrogatedinDC-specificCD/mice.Takentogether,theirresultsdefineamechanismofparacrineimmunoregulationoperatingbetweenadjacentDCsubsetsintheintestine.