Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 13, Pages 7305-7316Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1917834117
Keywords
lupus; interleukin-10; B cell help
Categories
Funding
- Fondazione Cariplo
- National Institute of Molecular Genetics Romeo ed Enrica Invernizzi
- Italian Lupus Foundation
- Long-Term European Molecular Biology Organization (EMBO) Fellowship
- Short-Term EMBO Fellowship
- Howard Hughes Medical Institute
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Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4(+)CCR6(+)IL-7R(+)T cells from human tonsils produced IL-10 following stimulation by naive B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6(+)B helper T cells were phenotypically distinct from follicular helper T (T-FH) cells and lacked BCL6 expression. In peripheral blood, a CCR6(+)T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation- associated surface markers. CD4(+)CCR6(+)T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4(+)CCR6(+)IL-7R(+)T cells were associated with the presence of pathogenic anti-dsDNA (double-stranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6(+)T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.
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