Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.
Détails
Télécharger: 32245990_BIB_BB3E78FC1719.pdf (3459.58 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_BB3E78FC1719
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.
Périodique
Scientific reports
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
03/04/2020
Peer-reviewed
Oui
Volume
10
Numéro
1
Pages
5851
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
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 <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
Oui
Création de la notice
25/04/2020 22:44
Dernière modification de la notice
30/04/2021 7:14