Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6⁺B helper T cells in systemic lupus erythematosus.

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 naïve 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 T_FH-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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