OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response.

TitleOX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response.
Publication TypeJournal Article
Year of Publication2015
AuthorsJacquemin 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
Date Published2015 Jun 16
KeywordsAdolescent, 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

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.

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Alternate JournalImmunity
PubMed ID26070486
PubMed Central IDPMC4570857
Grant ListU19-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

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