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Proc Natl Acad Sci U S A ; 117(13): 7305-7316, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-32184325

RESUMO

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.


Assuntos
Linfócitos B/imunologia , Interleucina-10/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Receptores CCR6/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Adulto , Animais , Formação de Anticorpos , Criança , Citocinas/imunologia , Humanos , Interleucina-10/biossíntese , Interleucina-17/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Tonsila Palatina/citologia , Tonsila Palatina/imunologia , Receptores CCR6/biossíntese , Células Th17/imunologia
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