| Title | OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Jacquemin C, Schmitt N, Contin-Bordes C, Liu Y, Narayanan P, Seneschal J, Maurouard T, Dougall D, Davizon ESpence, Dumortier H, Douchet I, Raffray L, Richez C, Lazaro E, Duffau P, Truchetet M-E, Khoryati L, Mercié P, Couzi L, Merville P, Schaeverbeke T, Viallard J-F, Pellegrin J-L, Moreau J-F, Muller S, Zurawski S, Coffman RL, Pascual V, Ueno H, Blanco P |
| Journal | Immunity |
| Volume | 42 |
| Issue | 6 |
| Pagination | 1159-70 |
| Date Published | 2015 Jun 16 |
| ISSN | 1097-4180 |
| Keywords | Adolescent, Adult, Aged, Antigen Presentation, B-Lymphocytes, Cell Differentiation, Cells, Cultured, Cytokines, Disease Progression, Female, Humans, Immunologic Memory, Inducible T-Cell Co-Stimulator Protein, Lupus Erythematosus, Systemic, Lymphocyte Activation, Male, Middle Aged, Molecular Targeted Therapy, Myeloid Cells, OX40 Ligand, Receptors, OX40, RNA, Signal Transduction, T-Lymphocytes, Helper-Inducer, Toll-Like Receptor 7, Young Adult |
| Abstract | 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(+) TÂ 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. |
| DOI | 10.1016/j.immuni.2015.05.012 |
| Custom 1 | |
| Alternate Journal | Immunity |
| PubMed ID | 26070486 |
| PubMed Central ID | PMC4570857 |
| Grant List | U19-AI057234 / AI / NIAID NIH HHS / United States U19-AI082715 / AI / NIAID NIH HHS / United States U19 AI057234 / AI / NIAID NIH HHS / United States U19-AI089987 / AI / NIAID NIH HHS / United States U19 AI082715 / AI / NIAID NIH HHS / United States U19 AI089987 / AI / NIAID NIH HHS / United States |