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

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-(TFH)-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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Lande R,Palazzo R,Gestermann N,Jandus C,Falchi M,Spadaro F,Riccieri V,James EA,Butera A,Boirivant M,Feldmeyer L,Surbeck I,Di Lucca J,Stuber F,Spinelli FR,Botti E,Marinari B,Bianchi L,Pica R,Cerbelli B,Giannakakis

doi

10.1038/s41598-020-62480-3

subject

Has Abstract

pub_date

2020-04-03 00:00:00

pages

5851

issue

1

issn

2045-2322

pii

10.1038/s41598-020-62480-3

journal_volume

10

pub_type

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