2022
mTORC1 Inhibition Protects Human Regulatory T Cells From Granzyme-B-Induced Apoptosis
Eskandari SK, Allos H, Al Dulaijan B, Melhem G, Sulkaj I, Alhaddad JB, Saad AJ, Deban C, Chu P, Choi JY, Kollar B, Pomahac B, Riella LV, Berger SP, Sanders JSF, Lieberman J, Li L, Azzi JR. mTORC1 Inhibition Protects Human Regulatory T Cells From Granzyme-B-Induced Apoptosis. Frontiers In Immunology 2022, 13: 899975. PMID: 35757726, PMCID: PMC9229986, DOI: 10.3389/fimmu.2022.899975.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisGranzymesHumansMechanistic Target of Rapamycin Complex 1MiceReceptors, Antigen, T-CellT-Lymphocytes, RegulatoryConceptsRegulatory T cellsT cellsHuman regulatory T cellsHost THumanized mouse modelPro-apoptotic pathwaysSkin allotransplantationClinical efficacyImmunosuppressive potencyIntracytoplasmic expressionTransplant fieldMouse modelCellular therapyHigh expressionTarget cellsRapamycin complex 1Lysosomal granulesFunctional effectsMechanistic targetPatientsApoptosisC-JunGranzymesDrug targetsS6K
2021
CD1a selectively captures endogenous cellular lipids that broadly block T cell response
Cotton R, Wegrecki M, Cheng T, Chen Y, Veerapen N, Le Nours J, Orgill D, Pomahac B, Talbot S, Willis R, Altman J, de Jong A, Van Rhijn I, Clark R, Besra G, Ogg G, Rossjohn J, Moody D. CD1a selectively captures endogenous cellular lipids that broadly block T cell response. Journal Of Experimental Medicine 2021, 218: e20202699. PMID: 33961028, PMCID: PMC8111460, DOI: 10.1084/jem.20202699.Peer-Reviewed Original ResearchMeSH KeywordsAntigen PresentationAntigens, CD1Cell LineCell MembraneHEK293 CellsHumansK562 CellsLymphocyte ActivationPhospholipidsReceptors, Antigen, T-CellT-LymphocytesConceptsNatural endogenous inhibitorsEndogenous lipidsCD1a proteinCellular lipidsT cell activationMembrane phospholipidsLonger lipidsSurface residuesEndogenous inhibitorLipidomics methodDetailed chemical structureCell activationLipidsCellsNatural blockerSphingolipidsDisplay platformProteinCrystal structureResiduesCell responsesBindingTetramerC42SphingomyelinImmunoregulatory and lipid presentation pathways are upregulated in human face transplant rejection
Win T, Crisler W, Dyring-Andersen B, Lopdrup R, Teague J, Zhan Q, Barrera V, Sui S, Tasigiorgos S, Murakami N, Chandraker A, Tullius S, Pomahac B, Riella L, Clark R. Immunoregulatory and lipid presentation pathways are upregulated in human face transplant rejection. Journal Of Clinical Investigation 2021, 131 PMID: 33667197, PMCID: PMC8262560, DOI: 10.1172/jci135166.Peer-Reviewed Original ResearchConceptsVCA rejectionTransplant rejectionT cellsTissue injuryGene expression profilingAntigen-presenting cell activationT-cell receptor sequencingSolid organ transplantsCell receptor sequencingT cell activation pathwaysAntigen-specific activationProliferative T cellsCell activation pathwaysNovo Nordisk FoundationAmerican SocietyExpression profilingFace transplant patientsTransplant patientsImmunologic pathwaysImmunoregulatory networkSkin biopsiesImmunomodulatory pathwaysLimb transplantsLundbeck FoundationTransplant ResearchHuman skin is colonized by T cells that recognize CD1a independently of lipid
Cotton R, Cheng T, Wegrecki M, Le Nours J, Orgill D, Pomahac B, Talbot S, Willis R, Altman J, de Jong A, Ogg G, Van Rhijn I, Rossjohn J, Clark R, Moody D. Human skin is colonized by T cells that recognize CD1a independently of lipid. Journal Of Clinical Investigation 2021, 131: e140706. PMID: 33393500, PMCID: PMC7773353, DOI: 10.1172/jci140706.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CD1HEK293 CellsHumansK562 CellsMembrane LipidsReceptors, Antigen, T-CellSkinT-LymphocytesConceptsT cellsSelf-lipid antigensSkin T cellsT cell autoreactivityT cell poolT cell repertoireMajor antigenic targetAntigenic targetsCell repertoireClinical diseaseCD1aSkin diseasesCD1 proteinsAntigenTCR recognitionCell poolEffector moleculesCD1a proteinLipid ligandsSmall antigensDiseaseHuman skinCellsAutoreactivityLipids