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 CCR6javax.xml.bind.JAXBElement@746419feT 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 (doublestranded 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.

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, C. Vasco, N. Gagliani, C. Cordiglieri, S. Mazzara, V. Ranzani, E. Rottoli, S. Curti, A. Penatti, B. Karnani, Y. Kobayashi, M. Crosti, M. Bombaci, J.P. Van Hamburg, G. Rossetti, R. Gualtierotti, M. Gerosa, S. Gatti, S. Torretta, L. Pignataro, S.W. Tas, S. Abrignani, M. Pagani, F. Grassi, P.L. Meroni, R.A. Flavell, J. Geginat. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 117:13(2020), pp. 7305-7316. [10.1073/pnas.1917834117]

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

Larghi P.;Bosotti R.;Vasco C.;Mazzara S.;Ranzani V.;Penatti A.;Bombaci M.;Gualtierotti R.;Gerosa M.;Torretta S.;Pignataro L.;Abrignani S.;Pagani M.;Geginat J.
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+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 CCR6javax.xml.bind.JAXBElement@746419feT 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 (doublestranded 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.
B cell help; Interleukin-10; Lupus
Settore MED/04 - Patologia Generale
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/730232
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