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Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6 + B helper T cells in systemic lupus erythematosus.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Mar 31; Vol. 117 (13), pp. 7305-7316. Date of Electronic Publication: 2020 Mar 17. - Publication Year :
- 2020
-
Abstract
- 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 <superscript>+</superscript> CCR6 <superscript>+</superscript> IL-7R <superscript>+</superscript> 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 <superscript>+</superscript> B helper T cells were phenotypically distinct from follicular helper T (T <subscript>FH</subscript> ) cells and lacked BCL6 expression. In peripheral blood, a CCR6 <superscript>+</superscript> T cell population with similar characteristics was identified, which lacked Th17- and T <subscript>FH</subscript> -associated gene signatures and differentiation-associated surface markers. CD4 <superscript>+</superscript> CCR6 <superscript>+</superscript> 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 <superscript>+</superscript> CCR6 <superscript>+</superscript> IL-7R <superscript>+</superscript> 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 <superscript>+</superscript> 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.<br />Competing Interests: Competing interest statement: J.G. is a consultant for Biotest for antiāIL-10 therapy in SLE patients.
- Subjects :
- Adult
Animals
Antibody Formation
Child
Cytokines immunology
Humans
Interleukin-10 biosynthesis
Interleukin-17 metabolism
Lupus Erythematosus, Systemic metabolism
Mice
Mice, Inbred C57BL
Palatine Tonsil cytology
Palatine Tonsil immunology
Receptors, CCR6 biosynthesis
Th17 Cells immunology
B-Lymphocytes immunology
Interleukin-10 immunology
Lupus Erythematosus, Systemic immunology
Receptors, CCR6 immunology
T-Lymphocytes, Helper-Inducer immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 117
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 32184325
- Full Text :
- https://doi.org/10.1073/pnas.1917834117