0000000000075372

AUTHOR

Andrea Gorzanelli

showing 4 related works from this author

A non-redundant role for OX40 in the competitive fitness of Treg in response to IL-2.

2010

OX40 stimulation is known to enhance activation of effector T cells and to inhibit induction and suppressive function of Treg. Here we uncovered a novel role of OX40 in sustaining Treg competitive fitness in vivo, during repopulation of lymphopenic hosts and reconstitution of BM chimeras. Defective expansion of OX40-null Treg diminished their ability to suppress inflammation in a model of lymphopenia-driven colitis. OX40-mediated promotion of Treg fitness spanned beyond lymphopenic environments, as endogenous Treg in OX40-null mice showed decreased accumulation during thymic development, enhanced susceptibility to antibody-mediated depletion and defective turnover following thymectomy. In v…

Malemedicine.medical_treatmentImmunologyBlotting Westernchemical and pharmacologic phenomenaEndogenyInflammationSuppressor of Cytokine Signaling ProteinsT-Lymphocytes RegulatoryMiceSuppressor of Cytokine Signaling 1 ProteinLymphopeniaOX40; Treg; IL-2.medicineSTAT5 Transcription FactorImmunology and AllergyAnimalsOX40PhosphorylationReceptorSTAT5Cell ProliferationMice KnockoutbiologyEffectorCell growthSuppressor of cytokine signaling 1hemic and immune systemsReceptors OX40IL-2.ColitisFlow Cytometrycytokinescompetitive fitnessSpecific Pathogen-Free OrganismsThymectomyMice Inbred C57BLTregRadiation ChimeraImmunologybiology.proteinInterleukin-2costimulatory moleculesmedicine.symptomcompetitive fitness; costimulatory molecules; cytokines; treg
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Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation

2009

Abstract The development of inflammatory diseases implies inactivation of regulatory T (Treg) cells through mechanisms that still are largely unknown. Here we showed that mast cells (MCs), an early source of inflammatory mediators, are able to counteract Treg inhibition over effector T cells. To gain insight into the molecules involved in their interplay, we set up an in vitro system in which all 3 cellular components were put in contact. Reversal of Treg suppression required T cell–derived interleukin-6 (IL-6) and the OX40/OX40L axis. In the presence of activated MCs, concomitant abundance of IL-6 and paucity of Th1/Th2 cytokines skewed Tregs and effector T cells into IL-17–producing T cel…

Regulatory T cellmedicine.medical_treatmentCellular differentiationImmunologyPriming (immunology)chemical and pharmacologic phenomenaMice TransgenicMast cell; T regulatory cell; Immune responseBiologyLymphocyte ActivationT-Lymphocytes RegulatoryBiochemistryImmune toleranceMiceMice CongenicmedicineImmune ToleranceMast CellT regulatory cellImmune responseCells CulturedCell ProliferationAnimalInterleukin-6Experimental autoimmune encephalomyelitisInterleukin-17hemic and immune systemsCell DifferentiationT lymphocyteT-Lymphocytes Helper-InducerHematologyCell BiologyReceptors OX40medicine.diseaseCell biologyMice Inbred C57BLmedicine.anatomical_structureCytokineImmunologyAnimals; Cell Differentiation; Cell Proliferation; Cells Cultured; Immune Tolerance; Interleukin-17; Interleukin-6; Lymphocyte Activation; Mast Cells; Membrane Glycoproteins; Mice; Mice Congenic; Mice Inbred C57BL; Mice Transgenic; Receptors OX40; Signal Transduction; T-Lymphocytes Helper-Inducer; T-Lymphocytes Regulatory; Tumor Necrosis Factors; Hematology; Biochemistry; Cell Biology; ImmunologyInterleukin 17Membrane GlycoproteinTumor Necrosis FactorSignal Transduction
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The matricellular protein SPARC supports follicular dendritic cell networking toward Th17 responses.

2011

Abstract Lymphnode swelling during immune responses is a transient, finely regulated tissue rearrangement, accomplished with the participation of the extracellular matrix. Here we show that murine and human reactive lymph nodes express SPARC in the germinal centres. Defective follicular dendritic cell networking in SPARC-deficient mice is accompanied by a severe delay in the arrangement of germinal centres and development of humoral autoimmunity, events that are linked to Th17 development. SPARC is required for the optimal and rapid differentiation of Th17 cells, accordingly we show delayed development of experimental autoimmune encephalomyelitis whose pathogenesis involves Th17. Not only h…

Autoimmune diseases; Extracellular matrix; Germinal centre reaction; Th17 cellsEncephalomyelitis Autoimmune ExperimentalMultiple SclerosisImmunologyCell CommunicationBiologyfollicular dendritic cellExtracellular matrixAnimals Genetically ModifiedMiceImmune systemSPARC; follicular dendritic cell; Th17Autoimmune diseasemedicinegerminal centre reactionImmunology and AllergyAnimalsHumansautoimmune diseasesOsteonectinMice KnockoutB-LymphocytesCD40Follicular dendritic cellsExperimental autoimmune encephalomyelitisMatricellular proteinGerminal centerSPARCCell Differentiationmedicine.diseaseCell biologyExtracellular MatrixImmunity HumoralMice Inbred C57BLCrosstalk (biology)Disease Models AnimalImmunologybiology.proteinDisease ProgressionTh17 CellsImmunizationMyelin-Oligodendrocyte GlycoproteinTh17autoimmune diseases; extracellular matrix; germinal centre reaction; th17 cellsDendritic Cells FollicularMyelin ProteinsJournal of autoimmunity
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Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient KitW-sh/W-sh mice

2011

Mast cell (MC)-deficient c-Kit mutant Kit(W/W-v) mice are protected against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, suggesting a detrimental role for MCs in this disease. To further investigate the role of MCs in EAE, we took advantage of a recently characterized model of MC deficiency, Kit(W-sh/W-sh). Surprisingly, we observed that myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE was exacerbated in Kit(W-sh/W-sh) compared with Kit(+/+) mice. Kit(W-sh/W-sh) mice showed more inflammatory foci in the central nervous system (CNS) and increased T-cell response against myelin. To understand whether the discrepant results obtaine…

Central Nervous SystemT-LymphocytesEncephalomyelitisexperimental autoimmune encephalomyelitismast cellsInbred C57BLSeverity of Illness IndeximmunologyMiceMyelinPeptide Fragmentimmune system diseasesMast CellEncephalomyelitisMyelin SheathbiologyExperimental autoimmune encephalomyelitisMast cellProto-Oncogene Proteins c-kitPhenotypemedicine.anatomical_structuremastcell-deficient miceBone Marrow Cellgenetics/immunology/pathology/prevention /&/ controlc-kit mutationsc-kit mutations; experimental autoimmune encephalomyelitis; granulocytes; mast cellsEncephalomyelitis Autoimmune ExperimentalCentral nervous systemBone Marrow CellsPathology and Forensic MedicineMyelin oligodendrocyte glycoproteinExperimentalAnimals Antibody Formation Bone Marrow Cells; pathology Central Nervous System; pathology Encephalomyelitis; Autoimmune; Experimental; genetics/immunology/pathology/prevention /&/ control Glycoproteins; immunology Granulocytes; pathology Immunization Mast Cells; pathology Mice Mice; Inbred C57BL Mutation Myelin Sheath; immunology Myelin-Oligodendrocyte Glycoprotein Peptide Fragments; immunology Phenotype Proto-Oncogene Proteins c-kit; deficiency/genetics/metabolism Severity of Illness Index T-Lymphocytes; pathologyAntigendeficiency/genetics/metabolismmedicineAnimalsMolecular BiologyGlycoproteinsAnimalMultiple sclerosismast-cell-deficient Kit W-sh/W-sh mice.Experimental autoimmune encephalomyelitis; mast-cell-deficient Kit W-sh/W-sh mice.GranulocytegranulocytesCell Biologymedicine.diseaseEncephalomyelitiExperimental autoimmune encephalomyelitiPeptide FragmentsMice Inbred C57BLT-LymphocyteAntibody FormationMutationImmunologybiology.proteinexperimental autoimmune encephalomyelitis; mastcell-deficient mice; mast cellspathologyImmunizationMyelin-Oligodendrocyte GlycoproteinGlycoproteinAutoimmuneLaboratory Investigation
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