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 cytometryA genomic meta-analysis of clinical variables and their association with intrinsic molecular subsets in systemic sclerosis
Franks JM, Toledo DM, Martyanov V, Wang Y, Huang S, Wood TA, Spino C, Chung L, Denton C, Derrett-Smith E, Gordon JK, Spiera R, Domsic R, Hinchcliff M, Khanna D, Whitfield ML. A genomic meta-analysis of clinical variables and their association with intrinsic molecular subsets in systemic sclerosis. Rheumatology 2022, 62: 19-28. PMID: 35751592, PMCID: PMC9788818, DOI: 10.1093/rheumatology/keac344.Peer-Reviewed Original ResearchConceptsMolecular subsetsIntrinsic subsetInflammatory subsetBaseline demographicsSSc patientsWhite/Caucasian patientsBaseline clinical demographicsAverage disease durationRodnan skin scoreAfrican American/BlackASSET trialUnique gene expression signatureDisease durationGene expression signaturesClinical demographicsParticipant seraSkin scoreSystemic sclerosisValidation cohortClinical variablesCaucasian patientsSpecific therapyAmerican/BlackSkin biopsiesDisease pathogenesis
2020
Mast cell activation in the systemic sclerosis esophagus
Tom K, Mehta BK, Hoffmann A, Aren K, Carns M, Lee J, Martyanov V, Popovich D, Kosarek N, Wood T, Brenner D, Carlson DA, Ostilla L, Willcocks E, Bryce P, Wechsler JB, Whitfield ML, Hinchcliff M. Mast cell activation in the systemic sclerosis esophagus. Journal Of Scleroderma And Related Disorders 2020, 6: 77-86. PMID: 34179507, PMCID: PMC8225255, DOI: 10.1177/2397198320941322.Peer-Reviewed Original ResearchMast cell numbersSSc patientsCell-directed therapiesSystemic sclerosisEsophageal biopsiesClinical parametersHealthy participantsCell numberNormal-like subsetsMast cell densityCell-targeted therapiesMast cell markersUseful therapeutic approachMast cell activationMast cell quantityRelevant clinical parametersMolecular classification systemEoE patientsEsophageal symptomsEosinophilic esophagitisUpper esophagusSkin biopsiesEntire esophagusMast cellsTherapeutic approachesCirculating classical monocytes share a common transcriptional signature with skin macrophages in Systemic Sclerosis
Makinde H, Dominguez S, Cuda C, Gadhvi G, Aren K, Zeng C, Eickelberg G, Khanna D, Assassi S, Frech T, Winter D, Perlman H, Hinchcliff M. Circulating classical monocytes share a common transcriptional signature with skin macrophages in Systemic Sclerosis. The Journal Of Immunology 2020, 204: 152.12-152.12. DOI: 10.4049/jimmunol.204.supp.152.12.Peer-Reviewed Original ResearchClassical monocytesSSc patientsSystemic sclerosisSkin macrophagesCommon transcriptional signatureEnd-organ fibrosisSystemic sclerosis cohortTranscriptional signatureSites of fibrosisPrecursors of macrophagesUpregulated genesSSc progressionProspective registryControl patientsProinflammatory moleculesSkin biopsiesPatientsMacrophage clustersMacrophagesMonocytesRespective controlsPrecursor populationSclerosisSignificant differencesFibrosis
2018
Mycophenolate Mofetil Treatment of Systemic Sclerosis Reduces Myeloid Cell Numbers and Attenuates the Inflammatory Gene Signature in Skin
Hinchcliff M, Toledo DM, Taroni JN, Wood TA, Franks JM, Ball MS, Hoffmann A, Amin SM, Tan AU, Tom K, Nesbeth Y, Lee J, Ma M, Aren K, Carns MA, Pioli PA, Whitfield ML. Mycophenolate Mofetil Treatment of Systemic Sclerosis Reduces Myeloid Cell Numbers and Attenuates the Inflammatory Gene Signature in Skin. Journal Of Investigative Dermatology 2018, 138: 1301-1310. PMID: 29391252, PMCID: PMC6590516, DOI: 10.1016/j.jid.2018.01.006.Peer-Reviewed Original ResearchConceptsMycophenolate mofetil treatmentMyeloid cell numbersMMF therapyMofetil treatmentSystemic sclerosisInflammatory scoreSkin biopsiesCell numberSkin myeloid cellsMyeloid dendritic cellsHalf of patientsRodnan skin scoreImmune cell numbersInflammatory gene signatureExpression of chemokinesProtein levelsCCL2 protein levelsCCL2 mRNA expressionInflammatory signatureDendritic cellsSkin scoreCCL2 mRNAEleven subjectsMonocyte migrationMyeloid cells
2014
FibronectinEDA Promotes Chronic Cutaneous Fibrosis Through Toll-Like Receptor Signaling
Bhattacharyya S, Tamaki Z, Wang W, Hinchcliff M, Hoover P, Getsios S, White ES, Varga J. FibronectinEDA Promotes Chronic Cutaneous Fibrosis Through Toll-Like Receptor Signaling. Science Translational Medicine 2014, 6: 232ra50. PMID: 24739758, PMCID: PMC4414050, DOI: 10.1126/scitranslmed.3008264.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Endogenous TLR4 ligandsCutaneous fibrosisTLR4 ligandToll-like receptor signalingProgressive autoimmune diseaseLesional skin biopsiesFibronectin extra domain ATreatment of fibrosisTissue repair responseHallmark of sclerodermaPersistent fibroblast activationExtra domain ATLR4 blockadeAutoimmune diseasesChronic conditionsChronic fibrosisReceptor 4Skin biopsiesFibrotic responseOrganotypic skin equivalentsMultiple organsPotent stimulusSclerodermaFibroblast activation
2012
Imatinib mesylate causes genome-wide transcriptional changes in systemic sclerosis fibroblasts in vitro.
Hinchcliff M, Huang CC, Ishida W, Fang F, Lee J, Jafari N, Wilkes M, Bhattacharyya S, Leof E, Varga J. Imatinib mesylate causes genome-wide transcriptional changes in systemic sclerosis fibroblasts in vitro. Clinical And Experimental Rheumatology 2012, 30: s86-96. PMID: 22691216, PMCID: PMC3860597.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesBiopsyCase-Control StudiesCells, CulturedFibroblastsFibrosisGene Expression ProfilingGene Expression RegulationHumansImatinib MesylateMiceMice, KnockoutOligonucleotide Array Sequence AnalysisPhosphorylationPiperazinesProtein Kinase InhibitorsProto-Oncogene Proteins c-ablPyrimidinesScleroderma, SystemicSignal TransductionSkinTime FactorsTranscription, GeneticTransforming Growth Factor beta1ConceptsSystemic sclerosisSSc fibroblastsSkin biopsiesInternal organ fibrosisHeterogeneous multifactorial diseaseControl fibroblastsControl skin biopsiesFibrotic gene expressionSystemic sclerosis fibroblastsC-AblProgressive skinAntifibrotic effectsImatinib mesylateHealthy controlsCardiovascular diseaseGene expressionHealthy subjectsFibrotic responseCholesterol metabolismOrgan fibrosisC-Abl activationMultifactorial diseaseTreatment resultsTissue levelsFibrosis