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

Sci Rep. 2020 Apr 3;10(1):5851. doi: 10.1038/s41598-020-62480-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Citrullinated Protein Antibodies / immunology
  • Antibodies, Antinuclear / immunology
  • Antibody Formation / immunology
  • Antimicrobial Cationic Peptides / immunology*
  • Autoantibodies / immunology*
  • Cathelicidins
  • DNA / immunology
  • Dendritic Cells / immunology
  • Female
  • Humans
  • Lupus Erythematosus, Systemic / etiology
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Psoriasis / etiology
  • Psoriasis / immunology
  • T-Lymphocytes / immunology*
  • Th17 Cells / immunology


  • Anti-Citrullinated Protein Antibodies
  • Antibodies, Antinuclear
  • Antimicrobial Cationic Peptides
  • Autoantibodies
  • DNA
  • Cathelicidins