Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.

Details

Serval ID
serval:BIB_BB3E78FC1719
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.
Journal
Scientific reports
Author(s)
Lande R., Palazzo R., Gestermann N., Jandus C., Falchi M., Spadaro F., Riccieri V., James E.A., Butera A., Boirivant M., Feldmeyer L., Surbeck I., Di Lucca J., Stuber F., Spinelli F.R., Botti E., Marinari B., Bianchi L., Pica R., Cerbelli B., Giannakakis K., Auteri S.E., Daniels I., Durrant L.G., Horstman S., Costanzo A., Romero P., Alessandri C., Conti F., Valesini G., Gilliet M., Chizzolini C., Frasca L.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
03/04/2020
Peer-reviewed
Oui
Volume
10
Number
1
Pages
5851
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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 <sub>FH</sub> )-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.
Pubmed
Open Access
Yes
Create date
25/04/2020 22:44
Last modification date
15/07/2020 6:26
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