All‐trans retinoic acid and rapamycin synergize with transforming growth factor‐β1 to induce regulatory T cells but confer different migratory capacities

[摘要] Tregsplayimportantrolesinmaintainingimmunehomeostasis,andthus,therapiesbasedonTregarepromisingcandidatesforthetreatmentforavarietyofimmune‐mediateddisorders.Thesetherapies,however,facethesignificantchallengeofobtainingadequatenumbersofTregsfromperipheralbloodthatmaintainssuppressivefunctionfollowingextensiveexpansion.InducingTregsfromnon‐Tregsoffersaviablealternative.DifferentmethodstoinduceTregshavebeenproposedandinvolvemainlytreatingcellswithTGF‐β‐iTreg.However,useofTGF‐βaloneisnotsufficienttoinducestableTregs.ATRAorrapahasbeenshowntosynergizewithTGF‐βtoinducestableTregs.WhereasTGF‐βplusRA‐iTregshavebeenwell‐describedintheliterature,thephenotype,function,andmigratorycharacteristicsofTGF‐βplusrapa‐iTreghaveyettobeelucidated.Herein,wedescribethephenotypeandfunctionofmouserapa‐iTregandrevealthatthesecellsdifferintheirinvivohomingcapacitywhencomparedwithmouseRA‐iTregandmouseTGF‐β‐iTreg.Thisdifferenceinmigratoryactivitysignificantlyaffectsthetherapeuticcapacityofeachsubsetinamousemodelofcolitis.WealsodescribethecharacteristicsofiTreggeneratedinthepresenceofTGF‐β,RA,andrapa...

[学科分类] 生理学

[关键词] Treg migration;chemokines;adoptive cell therapy;inflammatory bowel disease;live‐animal imaging