LL-37 levels are elevated in scleroderma patients and correlate with skin fibrosis severity, lung disease activity, and digital ulcers, suggesting the antimicrobial peptide may contribute to disease progression.
Serum LL-37 correlates with skin score, alveolitis, and digital ulcersThe antimicrobial peptide tracks with three key markers of scleroderma severity
What the researchers found
LL-37, the human antimicrobial peptide known primarily for fighting infections, was found to be significantly overexpressed in the skin of systemic sclerosis (SSc) patients — particularly in the small blood vessels of affected skin. Serum LL-37 levels were significantly higher in SSc patients than in healthy controls, and these levels correlated positively with skin fibrosis severity (skin score), alveolitis activity (lung inflammation), and the presence of digital ulcers. The study identified a molecular mechanism: deficiency of the transcription factor Fli1 drives LL-37 upregulation in endothelial cells, confirmed through gene silencing and chromatin immunoprecipitation. Mouse models of SSc (bleomycin-treated and Fli1+/- mice) showed similar upregulation of CRAMP, the mouse equivalent of LL-37.
Why it matters
Systemic sclerosis is a devastating autoimmune disease with limited treatment options, characterized by progressive skin fibrosis, blood vessel damage, and organ involvement. This study reveals that LL-37 — normally a protective antimicrobial peptide — may actually contribute to the disease process. Understanding this dual role could open new therapeutic strategies, potentially by modulating LL-37 levels to reduce fibrosis and vascular damage in SSc.
How the study worked
Combined human and mouse study. In human SSc skin, LL-37 expression was evaluated by immunostaining and quantitative RT-PCR. Serum LL-37 levels were measured by ELISA in SSc patients and healthy controls. Mechanistic studies used gene silencing and chromatin immunoprecipitation in human dermal microvascular endothelial cells to examine Fli1's regulation of the LL-37 gene (CAMP). Two mouse models were used: bleomycin-induced skin fibrosis and Fli1 heterozygous knockout mice.
Who was studied
Systemic sclerosis patients and healthy controls (humans); C57BL/6 mice (bleomycin model and Fli1+/- knockout)
What this study cannot tell us
While the study demonstrates strong correlations between LL-37 levels and disease severity, it does not prove that LL-37 directly causes fibrosis or vascular damage. The exact downstream mechanisms by which elevated LL-37 contributes to tissue pathology remain unclear. Sample sizes for the human serum analysis were not specified in the abstract.
How to read the evidence
Translational study combining human tissue and serum analysis with mouse models. Demonstrates strong correlations and a plausible molecular mechanism (Fli1 deficiency), but causation is not directly proven.
When this study was published
Published in 2016 in the British Journal of Dermatology. LL-37's role in autoimmune fibrotic diseases remains an active area of investigation.
The bigger picture
This study adds to a growing body of evidence that antimicrobial peptides do far more than fight infections. LL-37 has been linked to inflammatory conditions like psoriasis and rosacea, and now scleroderma joins the list. The finding that LL-37 correlates with multiple aspects of SSc severity — skin fibrosis, lung involvement, and vascular damage — suggests it may be a disease biomarker and possibly a therapeutic target. It also connects to broader research on Fli1 as a master regulator in SSc pathology.
Questions still open
- Could therapies that reduce LL-37 levels slow the progression of systemic sclerosis?
- Is serum LL-37 useful as a clinical biomarker for monitoring SSc disease activity?
- Does the LL-37–interferon-α feedback loop amplify autoimmune damage in scleroderma?
Common questions
Why would an antimicrobial peptide contribute to scleroderma?
Could LL-37 be used as a blood test for scleroderma severity?
Read the original research
A potential contribution of antimicrobial peptide LL-37 to tissue fibrosis and vasculopathy in systemic sclerosis.
The British journal of dermatology, 175(6), 1195-1203
Citation
Takahashi, T; Asano, Y; Nakamura, K; Yamashita, T; Saigusa, R; Ichimura, Y; Toyama, T; Taniguchi, T; Yoshizaki, A; Tamaki, Z; Tada, Y; Sugaya, M; Kadono, T; Sato, S. (2016). A potential contribution of antimicrobial peptide LL-37 to tissue fibrosis and vasculopathy in systemic sclerosis.. The British journal of dermatology, 175(6), 1195-1203. https://doi.org/10.1111/bjd.14699