title: Th1-Induced CD106 Expression Mediates Leukocytes Adhesion on Synovial Fibroblasts from Juvenile Idiopathic Arthritis Patients.
abstract: This study tested the hypothesis that subsets of human T helper cells can orchestrate leukocyte adhesion to synovial fibroblasts (SFbs), thus regulating the retention of leukocytes in the joints of juvenile idiopathic arthritis (JIA) patients. Several cell types, such as monocytes/macrophages, granulocytes, T and B lymphocytes, SFbs and osteoclasts participate in joint tissue damage JIA. Among T cells, an enrichment of classic and non-classic Th1 subsets, has been found in JIA synovial fluid (SF), compared to peripheral blood (PB). Moreover, it has been shown that IL-12 in the SF of inflamed joints mediates the shift of Th17 lymphocytes towards the non-classic Th1 subset. Culture supernatants of Th17, classic and non-classic Th1 clones, have been tested for their ability to stimulate proliferation, and to induce expression of adhesion molecules on SFbs, obtained from healthy donors. Culture supernatants of both classic and non-classic Th1, but not of Th17, clones, were able to induce CD106 (VCAM-1) up-regulation on SFbs. This effect, mediated by tumor necrosis factor (TNF)-α, was crucial for the adhesion of circulating leukocytes on SFbs. Finally, we found that SFbs derived from SF of JIA patients expressed higher levels of CD106 than those from healthy donors, resembling the phenotype of SFbs activated in vitro with Th1-clones supernatants. On the basis of these findings, we conclude that classic and non-classic Th1 cells induce CD106 expression on SFbs through TNF-α, an effect that could play a role in leukocytes retention in inflamed joints.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.|Regenerative Medicine Unit, Careggi University Hospital, Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Maggi
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Margheri
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Luciani
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Capone
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: Rossi
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Chillà
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Santarlasci
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.|Department of Clinical and Experimental Medicine and Centre for Biomolecular Studies Supporting Human Health, Second University of Naples, Naples, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Mazzoni
authors.affiliation: Department of Paediatrics, Rheumatology Unit, Anna Meyer Children's Hospital and University of Florence, Florence, Italy.
authors.forename: Rolando
authors.initials: R
authors.lastname: Cimaz
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Liotta
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Maggi
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cosmi
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Del Rosso
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.|Regenerative Medicine Unit, Careggi University Hospital, Florence, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Annunziato
mesh_terms: D000293:Adolescent; D000328:Adult; D001171:Arthritis, Juvenile / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D017746:Joint Capsule / Q000276:immunology* / Q000473:pathology; D008297:Male; D061251:Primary Cell Culture; D013582:Synovial Fluid / Q000166:cytology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*
chemical_list: D017077:Culture Media, Conditioned; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1