The Experts below are selected from a list of 144 Experts worldwide ranked by ideXlab platform
Flavia Castellano - One of the best experts on this subject based on the ideXlab platform.
-
The immunosuppressive enzyme il4i1 promoTes foxp3 RegulaTory T lymphocyTe differenTiaTion
European Journal of Immunology, 2015Co-Authors: Celine Cousin, Aude Aubatin, Sabine Le Gouvello, Lionel Apetoh, Flavia CastellanoAbstract:AbsTracT IL4I1 (inTerleukin-4-induced gene 1) is a phenylalanine oxidase produced mainly by APCs of myeloid origin, and converTs phenylalanine (Phe) To phenylpyruvaTe, hydrogen peroxide, and ammonia. We have previously shown ThaT IL4I1 is highly expressed by Tumor-associaTed macrophages from various human cancers and faciliTaTes immune evasion from The cyToToxic response in a murine Tumor model. Indeed, IL4I1 inhibiTs T-cell proliferaTion via hydrogen peroxide ToxiciTy on effecTor/memory T cells. Here, we explored The effecT of IL4I1 on naive CD4(+) T-cell differenTiaTion. We show ThaT IL4I1 sTimulaTes The generaTion of Foxp3(+) RegulaTory T (Treg) cells in viTro from human and mouse T cells. This effecT was observed wiTh IL4I1 from differenT sources, including The naTurally produced enzyme. Conversely, IL4I1 limiTs Th1 and Th2 polarizaTion while modifying The Th17 phenoType, in parTicular, by inducing iTs own producTion. Analysis of Treg-cell inducTion under condiTions of Phe deprivaTion and hydrogen peroxide addiTion suggesTs ThaT Phe consumpTion by The enzyme parTicipaTes in Treg-cell enrichmenT. In line wiTh This hypoThesis, IL4I1 inhibiTs mTORC1 signaling shorTly afTer T-cell acTivaTion. Thus, The IL4I1 enzyme may acT on T cells boTh by direcT inhibiTion of effecTor cell proliferaTion and by indirecT immunoregulaTion mediaTed by Treg-cell inducTion.
Joost Van Meerwijk - One of the best experts on this subject based on the ideXlab platform.
-
CD4(+)CD25(+) RegulaTory T lymphocyTes in bone marrow TransplanTaTion.
Seminars in Immunology, 2006Co-Authors: Olivier Joffre, Joost Van MeerwijkAbstract:InducTion of immunological Tolerance To alloanTigens would be The TreaTmenT of choice To prevenT grafT-versus-hosT disease (GvHD) and allografT rejecTion in TransplanTaTion medicine. Organisms use a varieTy of mechanisms To avoid poTenTially deadly immuniTy To self-anTigens. The mosT poTenT self-Tolerance mechanism is probably dominanT Tolerance assured by RegulaTory and suppressor T lymphocyTes. IT appears Therefore aTTracTive To use The same mechanism To induce TransplanTaTion-Tolerance. We here review and discuss recenT advances in The use of one of The besT-characTerized RegulaTory T lymphocyTe populaTions, CD4(+)CD25(+) T cells, To prevenT grafT-versus-hosT disease and bone marrow allografT rejecTion.
-
GeneTic conTrol of Thymic developmenT of CD4+CD25+FoxP3+ RegulaTory T lymphocyTes.
European Journal of Immunology, 2005Co-Authors: Paola Romagnoli, Julie Tellier, Joost Van MeerwijkAbstract:Among The several mechanisms known To be involved in The esTablishmenT and mainTenance of immunological Tolerance, The acTiviTy of CD4+CD25+ RegulaTory T lymphocyTes has recenTly inciTed mosT inTeresT because of iTs criTical role in inhibiTion of auToimmuniTy and anTi-Tumor immuniTy. Surprisingly, very liTTle is known abouT poTenTial geneTic modulaTion of inTraThymic RegulaTory T lymphocyTe developmenT. We show ThaT disTincT proporTions of CD4+CD25+FoxP3+ RegulaTory T cells are found in Thymi of common laboraTory mouse sTrains. We demonsTraTe ThaT disTincT levels of phenoTypically idenTical RegulaTory T cells develop wiTh similar kineTics in The mice sTudied. Our experimenTal daTa on congenic mouse sTrains indicaTe ThaT differences are noT caused by The disTincT MHC haploTypes of The inbred mouse sTrains. Moreover, The responsible loci acT in a ThymocyTe-inTrinsic manner, confirming The laTTer conclusion. We have noT found any correlaTion beTween Thymic and peripheral levels of RegulaTory T cells, consisTenT wiTh known homeosTaTic expansion and/or reTracTion of The peripheral RegulaTory T cell pool. Our daTa indicaTe ThaT polymorphic genes modulaTe differenTiaTion of RegulaTory T cells. IdenTificaTion of responsible genes may reveal novel clinical TargeTs and sTill elusive RegulaTory T cell-specific markers. ImporTanTly, These genes may also modulaTe suscepTibiliTy To auToimmune disease.
Celine Cousin - One of the best experts on this subject based on the ideXlab platform.
-
The immunosuppressive enzyme il4i1 promoTes foxp3 RegulaTory T lymphocyTe differenTiaTion
European Journal of Immunology, 2015Co-Authors: Celine Cousin, Aude Aubatin, Sabine Le Gouvello, Lionel Apetoh, Flavia CastellanoAbstract:AbsTracT IL4I1 (inTerleukin-4-induced gene 1) is a phenylalanine oxidase produced mainly by APCs of myeloid origin, and converTs phenylalanine (Phe) To phenylpyruvaTe, hydrogen peroxide, and ammonia. We have previously shown ThaT IL4I1 is highly expressed by Tumor-associaTed macrophages from various human cancers and faciliTaTes immune evasion from The cyToToxic response in a murine Tumor model. Indeed, IL4I1 inhibiTs T-cell proliferaTion via hydrogen peroxide ToxiciTy on effecTor/memory T cells. Here, we explored The effecT of IL4I1 on naive CD4(+) T-cell differenTiaTion. We show ThaT IL4I1 sTimulaTes The generaTion of Foxp3(+) RegulaTory T (Treg) cells in viTro from human and mouse T cells. This effecT was observed wiTh IL4I1 from differenT sources, including The naTurally produced enzyme. Conversely, IL4I1 limiTs Th1 and Th2 polarizaTion while modifying The Th17 phenoType, in parTicular, by inducing iTs own producTion. Analysis of Treg-cell inducTion under condiTions of Phe deprivaTion and hydrogen peroxide addiTion suggesTs ThaT Phe consumpTion by The enzyme parTicipaTes in Treg-cell enrichmenT. In line wiTh This hypoThesis, IL4I1 inhibiTs mTORC1 signaling shorTly afTer T-cell acTivaTion. Thus, The IL4I1 enzyme may acT on T cells boTh by direcT inhibiTion of effecTor cell proliferaTion and by indirecT immunoregulaTion mediaTed by Treg-cell inducTion.
Yoann Rombouts - One of the best experts on this subject based on the ideXlab platform.
-
Colon-specific immune microenvironmenT regulaTes cancer progression versus rejecTion
OncoImmunology, 2020Co-Authors: Giulia Trimaglio, Anne-françoise Tilkin-mariamé, Virginie Feliu, Françoise Lauzéral-vizcaino, Marie Tosolini, Carine Valle, Maha Ayyoub, Olivier Neyrolles, Nathalie Vergnolle, Yoann RomboutsAbstract:ImmunoTherapies have achieved clinical benefiT in many Types of cancer buT remain limiTed To a subseT of paTienTs in colorecTal cancer (CRC). ResisTance To immunoTherapy can be aTTribuTed in parT To Tissuespecific facTors consTraining anTiTumor immuniTy. Thus, a beTTer undersTanding of how The colon microenvironmenT shapes The immune response To CRC is needed To idenTify mechanisms of resisTance To immunoTherapies and guide The developmenT of novel TherapeuTics. In an orThoTopic mouse model of MC38-CRC, Tumor progression was moniTored by bioluminescence imaging and The immune signaTures were assessed aT a TranscripTional level using NanoSTring and aT a cellular level by flow cyTomeTry. DespiTe iniTial Tumor growTh in all mice, only 25% To 35% of mice developed a progressive leThal CRC while The remaining animals sponTaneously rejecTed Their solid Tumor. No Tumor rejecTion was observed in The absence of adapTive immuniTy, nor when MC38 cells were injecTed in non-orThoTopic locaTions, subcuTaneously or inTo The liver. We observed ThaT progressive CRC Tumors exhibiTed a proTumor immune response, characTerized by a RegulaTory T-lymphocyTe paTTern, discernible shorTly posT-Tumor implanTaTion, as well as suppressive myeloid cells. In conTrasT, Tumor-rejecTing mice presenTed an early inflammaTory response and an anTiTumor microenvironmenT enriched in CD8+ T cells. Taken TogeTher, our daTa demonsTraTe The role of The colon microenvironmenT in regulaTing The balance beTween anTi or proTumor immune responses. While emphasizing The relevance of The CRC orThoTopic model, They seT The basis for exploring The impacT of The idenTified signaTures in colon cancer response To immunoTherapy.
Lionel Apetoh - One of the best experts on this subject based on the ideXlab platform.
-
The immunosuppressive enzyme il4i1 promoTes foxp3 RegulaTory T lymphocyTe differenTiaTion
European Journal of Immunology, 2015Co-Authors: Celine Cousin, Aude Aubatin, Sabine Le Gouvello, Lionel Apetoh, Flavia CastellanoAbstract:AbsTracT IL4I1 (inTerleukin-4-induced gene 1) is a phenylalanine oxidase produced mainly by APCs of myeloid origin, and converTs phenylalanine (Phe) To phenylpyruvaTe, hydrogen peroxide, and ammonia. We have previously shown ThaT IL4I1 is highly expressed by Tumor-associaTed macrophages from various human cancers and faciliTaTes immune evasion from The cyToToxic response in a murine Tumor model. Indeed, IL4I1 inhibiTs T-cell proliferaTion via hydrogen peroxide ToxiciTy on effecTor/memory T cells. Here, we explored The effecT of IL4I1 on naive CD4(+) T-cell differenTiaTion. We show ThaT IL4I1 sTimulaTes The generaTion of Foxp3(+) RegulaTory T (Treg) cells in viTro from human and mouse T cells. This effecT was observed wiTh IL4I1 from differenT sources, including The naTurally produced enzyme. Conversely, IL4I1 limiTs Th1 and Th2 polarizaTion while modifying The Th17 phenoType, in parTicular, by inducing iTs own producTion. Analysis of Treg-cell inducTion under condiTions of Phe deprivaTion and hydrogen peroxide addiTion suggesTs ThaT Phe consumpTion by The enzyme parTicipaTes in Treg-cell enrichmenT. In line wiTh This hypoThesis, IL4I1 inhibiTs mTORC1 signaling shorTly afTer T-cell acTivaTion. Thus, The IL4I1 enzyme may acT on T cells boTh by direcT inhibiTion of effecTor cell proliferaTion and by indirecT immunoregulaTion mediaTed by Treg-cell inducTion.