Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.
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3 avril 2020
- doi: 10.1038/s41598-020-62480-3
- issn: 2045-2322
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info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-020-62480-3
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info:eu-repo/semantics/altIdentifier/pmid/32245990
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_BB3E78FC17195
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
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Lupus erythematosus disseminatus SLE (Disease) Libman-Sacks disease Lupus erythematosus, Systemic Lupus (Systemic lupus erythematosus)Citer ce document
R. Lande et al., « Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus. », Serveur académique Lausannois, ID : 10.1038/s41598-020-62480-3
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Résumé
LL37 exerts a dual pathogenic role in psoriasis. Bound to self-DNA/RNA, LL37 licenses autoreactivity by stimulating plasmacytoid dendritic cells-(pDCs)-Type I interferon (IFN-I) and acts as autoantigen for pathogenic Th17-cells. In systemic lupus erythematosus (SLE), LL37 also triggers IFN-I in pDCs and is target of pathogenic autoantibodies. However, whether LL37 activates T-cells in SLE and how the latter differ from psoriasis LL37-specific T-cells is unknown. Here we found that 45% SLE patients had circulating T-cells strongly responding to LL37, which correlate with anti-LL37 antibodies/disease activity. In contrast to psoriatic Th17-cells, these LL37-specific SLE T-cells displayed a T-follicular helper-(T FH )-like phenotype, with CXCR5/Bcl-6 and IL-21 expression, implicating a role in stimulation of pathogenic autoantibodies. Accordingly, SLE LL37-specific T-cells promoted B-cell secretion of pathogenic anti-LL37 antibodies in vitro. Importantly, we identified abundant citrullinated LL37 (cit-LL37) in SLE tissues (skin and kidney) and observed very pronounced reactivity of LL37-specific SLE T-cells to cit-LL37, compared to native-LL37, which was much more occasional in psoriasis. Thus, in SLE, we identified LL37-specific T-cells with a distinct functional specialization and antigenic specificity. This suggests that autoantigenic specificity is independent from the nature of the autoantigen, but rather relies on the disease-specific milieu driving T-cell subset polarization and autoantigen modifications.