THU0221 EVIDENCE FOR A PATHOGENIC ROLE OF EXTRA-FOLLICULAR, IL-10 PRODUCING CCR6+B-HELPER T-CELLS IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: M. Gerosa, F. Facciotti, P. Larghi, R. Bosotti, C. Vasco, N. Gagliani, C. Cordiglieri, E. Rottoli, A. E. Penatti, L. M. Argolini, B. Karnani, Y. Kobayashi, M. Bombaci, J. P. Van Hamburg, R. Gualtierotti, S. Gatti, S. Torretta, L. Pignataro, S. W. Tas, R. Caporali, S. Abrignani, M. Pagani, F. Grassi, P. L. Meroni, R. Flavell, J. Geginat
Journal: Annals of the Rheumatic Diseases (2020)

Background: IL-10 plays a key role in systemic lupus erythematosus (SLE) pathogenesis, promoting B-cell response. IL10 is mainly secreted by regulatory T-cells, but follicular helper T-cells (T FH ), also produce it. We previously identified a subset of CCR6 + IL-7R + T-cells in human tonsils providing IL-10-dependent B-cell help. These CCR6 + T-cells were able to produce IL-10, inducing IgG production. Objectives: to investigate a possible role of CD4 + CCR6 + IL7R + T-cells in SLE pathogenesis. Methods: 37 patients fulfilling the ACR criteria for SLE have been included. Disease activity was assessed by 2k-SLEDAI. PBMC were analyzed by flow cytometry, using specific lineage markers. CCR6 + IL7R + T-cells purified from total PBMC of SLE patients or healthy donors (HD) were co-cultured with autologous CD20 + B-cells. IL-10, Il-17, total IgG and anti-dsDNA antibodies titers in patients serum and culture supernatants were assessed by ELISA. Embedded sections of lymph nodes from 8 SLE patients were analyzed by immunofluorescence (IF). Results: IL10 levels were significantly higher in SLE patients (Fig 1A). CD4 + CCR6 + IL7R + T-cells were significantly increased in SLE, in particular in those with higher disease activity and higher IL10 levels. CD4 + CCR6 + IL7R + T-cells levels associated with anti-dsDNA positivity. CCR6 + IL7R + T-cells of SLE patients induced production of IgG and anti-dsDNA IgG (in anti-dsDNA + patients) from autologous B-cells, providing spontaneous help for autoantibody production ex vivo (Fig 1B-C). The IF study of lymph nodes of SLE patients showed that IL-10-producing CCR6 + T-cells were highly abundant and co-localized with B-cells at follicle margins. Fig 1 Conclusion: our study revealed a novel population of extra-follicular B-helper T-cells, which produce IL-10 and could play a prominent pathogenic role in SLE. Further studies will clarify if this potentially pathogenic cell population might represent a possible future therapeutic target. References: [1]Facciotti F. J Allergy Clin Immunol. 2016; Geginat J. Semin Immunol. 2019; Tsokos GC. Nat Rev Rheumatol. 2019 Tab 1: SLE patients characteristics (n=37) Demographics Female/Male, n 37/5 Age, years, median (IQR) 44 (38-49) Disease duration, years, median (IQR) 19 (11-26) Lab tests ANA 86% *anti-dsDNA (%) 46% medium/high titre 41% Disease activity and clinical manifestations SLEDAI-2K, median (min-max) 3.5 (0-24) Moderate/high activity 19% Ongoing therapy Prednisone dose mg/day, median (IQR) 7,5 mg (2,5 – 20) hydroxychloroquine 78% Immunosuppressants 87% Fig 2 Disclosure of Interests: : Maria Gerosa: None declared, Federica Facciotti: None declared, Paola Larghi: None declared, Roberto Bosotti: None declared, Chiara Vasco: None declared, Nicola Gagliani: None declared, Chiara Cordiglieri: None declared, Elsa Rottoli: None declared, Alessandra Emiliana Penatti: None declared, Lorenza Maria Argolini: None declared, Bhavna Karnani: None declared, Yasushi Kobayashi: None declared, Mauro Bombaci: None declared, Jan Piet Van Hamburg: None declared, Roberta Gualtierotti: None declared, Stefano Gatti: None declared, Sara Torretta: None declared, Lorenzo Pignataro: None declared, Sander W. Tas: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp &amp; Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Sergio Abrignani: None declared, Massimiliano Pagani: None declared, Fabio Grassi: None declared, Pier Luigi Meroni: None declared, Richard Flavell: None declared, Jens Geginat: None declared