2023
IL-6 trans-signaling in a humanized mouse model of scleroderma
Odell I, Agrawal K, Sefik E, Odell A, Caves E, Kirkiles-Smith N, Horsley V, Hinchcliff M, Pober J, Kluger Y, Flavell R. IL-6 trans-signaling in a humanized mouse model of scleroderma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2306965120. PMID: 37669366, PMCID: PMC10500188, DOI: 10.1073/pnas.2306965120.Peer-Reviewed Original ResearchConceptsBone marrow-derived immune cellsIL-6Human hematopoietic stem cellsImmune cellsT cellsScleroderma skinSoluble IL-6 receptorCD8 T cellsHumanized mouse modelPathogenesis of sclerodermaMesenchymal cellsFibroblast-derived IL-6IL-6 receptorIL-6 signalingT cell activationHuman IL-6Human T cellsExpression of collagenFibrosis improvementPansclerotic morpheaHuman endothelial cellsHumanized miceReduced markersSkin graftsHuman CD4
2022
Human dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis
Bhandari R, Yang H, Kosarek NN, Smith AE, Garlick JA, Hinchcliff M, Whitfield ML, Pioli PA. Human dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis. Rheumatology 2022, 62: si114-si124. PMID: 35946522, PMCID: PMC9910573, DOI: 10.1093/rheumatology/keac453.Peer-Reviewed Original ResearchConceptsFibroblast-derived exosomesSSc patientsMacrophage activationGender-matched control subjectsSSc fibroblastsDonor-derived macrophagesReciprocal activationUpregulated surface expressionMHC class IICo-cultured macrophagesHealthy control fibroblastsExtracellular matrix depositionCell typesSystemic sclerosisHealthy ageIL-10Production of collagenIL-12p40IL-6Control subjectsSkin biopsiesSSc skinTherapeutic targetingClass IIFlow cytometry
2020
Pro-fibrotic Activation of Human Macrophages in Systemic Sclerosis
Bhandari R, Ball M, Martyanov V, Popovich D, Schaafsma E, Han S, Eltanbouly M, Carns M, Arroyo E, Aren K, Hinchcliff M, Whitfield M, Pioli P. Pro-fibrotic Activation of Human Macrophages in Systemic Sclerosis. The Journal Of Immunology 2020, 204: 224.33-224.33. DOI: 10.4049/jimmunol.204.supp.224.33.Peer-Reviewed Original ResearchSystemic sclerosisSSc patientsIL-6IL-6 blockadeHealthy donor monocytesMediator of fibrosisFibrotic activationSSc tissuesInflammatory signatureDonor monocytesPatient macrophagesHealthy donorsTherapeutic targetingBasal conditionsSoluble factorsHuman macrophagesSurface markersMacrophagesPatient's skinElevated levelsGene expression profilesSclerosisPatientsFibrosisImmunophenotype
2018
SAT0486 Myeloablation followed by autologous stem cell rescue leads to normalisation of serum il-6 levels in patients with systemic sclerosis
Bellocchi C, Sullivan K, Goldmuntz E, Ying J, Keyes-Elstein L, Varga J, Hinchcliff M, McSweeney P, Furst D, Nash R, Crofford L, Welch B, Pinckney A, Mayes M, Assassi S. SAT0486 Myeloablation followed by autologous stem cell rescue leads to normalisation of serum il-6 levels in patients with systemic sclerosis. Annals Of The Rheumatic Diseases 2018, 77: 1100. DOI: 10.1136/annrheumdis-2018-eular.3731.Peer-Reviewed Original ResearchSerum IL-6 levelsHematopoietic stem cell transplantationIL-6 levelsStem cell transplantationSystemic sclerosisIL-6IL-12IL-1βSCOT trialDisease durationSSc pathogenesisAutologous hematopoietic stem cell transplantationPro-inflammatory Th1 cytokinesAutologous stem cell rescueAutologous stem cell transplantationSerum IFN-γ levelsBaseline clinical featuresMean disease durationStem cell rescueRodnan skin scoreSerum IL-6Diffuse systemic sclerosisMajority of patientsAvailable serum samplesIFN-γ levels