Fiche publication
Date publication
juin 2015
Journal
Immunity
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MULLER Sylviane
,
Dr DUMORTIER Hélène
Tous les auteurs :
Jacquemin C, Schmitt N, Contin-Bordes C, Liu Y, Narayanan P, Seneschal J, Maurouard T, Dougall D, Davizon ES, Dumortier H, Douchet I, Raffray L, Richez C, Lazaro E, Duffau P, Truchetet ME, Khoryati L, Mercié P, Couzi L, Merville P, Schaeverbeke T, Viallard JF, Pellegrin JL, Moreau JF, Muller S, Zurawski S, Coffman RL, Pascual V, Ueno H, Blanco P
Lien Pubmed
Résumé
Increased activity of T follicular helper (Tfh) cells plays a major pathogenic role in systemic lupus erythematosus (SLE). However, the mechanisms that cause aberrant Tfh cell responses in SLE remain elusive. Here we showed the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE. OX40L was expressed by myeloid antigen-presenting cells (APCs), but not B cells, in blood and in inflamed tissues in adult and pediatric SLE patients. The frequency of circulating OX40L-expressing myeloid APCs positively correlated with disease activity and the frequency of ICOS(+) blood Tfh cells in SLE. OX40 signals promoted naive and memory CD4(+) T cells to express multiple Tfh cell molecules and were sufficient to induce them to become functional B cell helpers. Immune complexes containing RNA induced OX40L expression on myeloid APCs via TLR7 activation. Our study provides a rationale to target the OX40L-OX40 axis as a therapeutic modality for SLE.
Mots clés
Adolescent, Adult, Aged, Antigen Presentation, B-Lymphocytes, immunology, Cell Differentiation, Cells, Cultured, Cytokines, metabolism, Disease Progression, Female, Humans, Immunologic Memory, Inducible T-Cell Co-Stimulator Protein, metabolism, Lupus Erythematosus, Systemic, immunology, Lymphocyte Activation, Male, Middle Aged, Molecular Targeted Therapy, Myeloid Cells, immunology, OX40 Ligand, metabolism, RNA, immunology, Receptors, OX40, metabolism, Signal Transduction, T-Lymphocytes, Helper-Inducer, immunology, Toll-Like Receptor 7, metabolism, Young Adult
Référence
Immunity. 2015 Jun;42(6):1159-70
