Characterization of circulating extracellular traps and immune responses to citrullinated LL37 in psoriasis.

Background

The DNA-binding peptide LL37 is a suspected autoantigen in psoriasis. It can be found in neutrophil extracellular traps (NETs) which have been suggested to play a role in the pathogenesis of the disease. Citrullination, the conversion of peptidyl-arginine into peptidyl-citrulline, can be implicated in the formation of NETs. We hypothesized that citrullination increases LL37 immunogenicity and that NETs are a source of LL37.

Objectives

We aimed to characterize cytokine responses of B cells and T cells to native and citrullinated LL37 (citLL37) and determine the prevalence and composition of circulating NETs in patients with psoriasis and healthy blood donors (HDs).

Methods

Mononuclear cells (MNCs) and serum were isolated from 20 HDs and 20 patients with psoriasis. The MNCs were stimulated with native LL37 and citLL37 and the proportion of cytokine-positive B cells and T cells was determined by flow cytometry. Circulating antibodies against native LL37 and citLL37 as well as circulating NETs were measured by ELISA, as was the content of LL37, citLL37, and IgG in the NETs.

Results

CitLL37, but not native LL37, induced IFN-γ-production by T cells and B cells from psoriasis patients, as well as IL-10-production by the patients' CD4

Conclusion

Citrullinated but not native LL37 elicits IFN-γ-responses by T cells and B cells from psoriasis patients, particularly those with circulating NETs and early disease onset, suggesting a role of citLL37 as an autoantigen in this subgroup of patients.

Informations de copyright

Copyright © 2023 Martín Monreal, Kvist-Hansen, Massarenti, Steffensen, Loft, Hansen, Ødum, Skov and Nielsen.

Déclaration de conflit d'intérêts

Outside of the submitted work: NL has been an honorary speaker for Eli Lilly, Janssen Cilag, and Sandoz. LS has received research funding from Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, Sanofi, Almirall, the Danish National Psoriasis Foundation, the LEO Foundation and honoraria as consultant and/or speaker for AbbVie, Eli Lilly, Novartis, Pfizer, LEO Pharma, Janssen, UCB, Almirall, Bristol-Myers Squibb, and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.