biostudies-literatureBhandari REstablished Investigator Research GrantsNCATS NIH HHSNational Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases Small Business Innovative Research GrantsNIAID NIH HHSNational Institutes of HealthNational Institute of General Medical SciencesJohn Osborn Polak EndowmentGeisel School of Medicine at Dartmouth’s Center for Quantitative BiologyNCI NIH HHSScleroderma Research FoundationNIAMS NIH HHSScleroderma FoundationNIGMS NIH HHSSI114-SI124https://www.ebi.ac.uk/biostudies/studies/S-EPMC9910573biostudies-literatureUnknown62(SI)<h4>Objectives</h4>Prior work demonstrates that co-cultured macrophages and fibroblasts from patients with SSc engage in reciprocal activation. However, the mechanism by which these cell types communicate and contribute to fibrosis and inflammation in SSc is unknown.<h4>Methods</h4>Fibroblasts were isolated from skin biopsies obtained from 7 SSc patients or 6 healthy age and gender-matched control subjects following written informed consent. Human donor-derived macrophages were cultured with exosomes isolated from control or SSc fibroblasts for an additional 48 h. Macrophages were immunophenotyped using flow cytometry, qRT-PCR and multiplex. For mutual activation studies, exosome-activated macrophages were co-cultured with SSc or healthy fibroblasts using Transwells.<h4>Results</h4>MacrophRheumatology (Oxford, England)Human dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis.PMC9910573R43 AR072170P30 CA023108R21 AI169420R44 AR0721702R44AR072170-02P20 GM130454UL1 TR001863Yang HHinchcliff MBhandari RKosarek NNPioli PAWhitfield MLSmith AEGarlick JAfalseHuman dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis.<h4>Objectives</h4>Prior work demonstrates that co-cultured macrophages and fibroblasts from patients with SSc engage in reciprocal activation. However, the mechanism by which these cell types communicate and contribute to fibrosis and inflammation in SSc is unknown.<h4>Methods</h4>Fibroblasts were isolated from skin biopsies obtained from 7 SSc patients or 6 healthy age and gender-matched control subjects following written informed consent. Human donor-derived macrophages were cultured with exosomes isolated from control or SSc fibroblasts for an additional 48 h. Macrophages were immunophenotyped using flow cytometry, qRT-PCR and multiplex. For mutual activation studies, exosome-activated macrophages were co-cultured with SSc or healthy fibroblasts using Transwells.<h4>Results</h4>Macroph2023-01-01T00:00:00Z2023 Feb2025-04-04T20:04:19.962Z2025-04-04T20:04:19.962ZS-EPMC99105733594652210.1093/rheumatology/keac453