Evidence for a pathogenic role of extrafollicular, IL-10–producing CCR6+B helper T cells in systemic lupus erythematosus
F Facciotti, P Larghi, R Bosotti… - Proceedings of the …, 2020 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2020•National Acad Sciences
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 (TFH) cells and lacked BCL6 expression.
In peripheral blood, a CCR6+ T cell population with similar characteristics was identified …
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 (TFH) cells and lacked BCL6 expression.
In peripheral blood, a CCR6+ T cell population with similar characteristics was identified …
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 (TFH) 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.
National Acad Sciences
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