Journal
IMMUNITY
Volume 42, Issue 6, Pages 1159-1170Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2015.05.012
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Funding
- Centre national pour la Recherche Scientifique
- Societe Francaise de Rhumatologie
- Arthritis Fondation Courtin
- Ministere de la Recherche et de l'Enseignement superieur
- NIH [U19-AI057234, U19-AI082715, U19-AI089987]
- Alliance for Lupus Research
- Baylor Health Care System
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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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