Cathelicidin LL-37: A new important molecule in the pathophysiology of systemic lupus erythematosus.
Moreno-Angarita. Alejandro A; Aragón. Cristian C CC; Tobón. Gabriel J GJ
Key Findings
- LL-37 can form complexes with DNA that activate plasmacytoid dendritic cells via FcÎłRII and TLR9.
- Activated pDCs produce excess type I interferon, a key driver of systemic lupus erythematosus.
- LL-37 and anti‑LL‑37 antibodies are detectable in SLE patients, suggesting potential as disease biomarkers.
Practical Outcomes
- For most biohackers, this research is mainly of interest if you have lupus or an autoimmune condition. It highlights LL-37 as a possible biomarker to monitor disease activity, but it does not provide any dosage, supplement, or protocol recommendations. Until therapeutic strategies targeting LL-37 are developed, there’s no direct action to take.
Summary
LL-37 is a natural antimicrobial peptide that also messes with the immune system. In lupus patients it can bind DNA and form complexes that trigger immune cells (pDCs) to release a lot of type I interferon, which fuels the disease. This makes LL-37 a possible marker for lupus activity, but the paper doesn’t give any tips on how to use it for health hacks.
Abstract
Cathelicidin LL-37 is an antimicrobial peptide that is synthesized by epithelial cells, neutrophils, or lymphocytes and act as an essential defense mechanism against bacterial, viral, or fungi infection of eukaryotic organisms. However, in recent years, this cathelicidin has gained the interest of the scientific community because, besides its antimicrobial properties, LL-37 is an immunomodulator that can contribute to the development of autoimmune diseases. The other non-antimicrobial function of this cathelicidin is its ability to form complexes with the DNA, stimulating plasmacytoid dendritic cells (pDCs) to produce type I IFN, deciding the course of autoimmune diseases, including systemic lupus erythematosus (SLE). The chronic activation of pDCs by surrounding complexes is a crucial factor for the early development of autoimmunity in SLE patients. This stimulation is given by the complexes (LL-37-DNA/anti-DNA) recognized by the receptor FcγRII on pDCs, allowing its endocytosis and its recognition via TLR9, leading to the activation of pDCs and enhanced type I IFN production. In this article, we reviewed the structure, function, and importance of LL-37 in innate immunity, as well as its biological plausibility in the pathophysiology of autoimmune diseases such as SLE. In this narrative review, we included primary journal articles describing the function, structure, prevalence, and importance of LL-37 in various manifestations of SLE, as well as LL-37 and anti-LL37 antibodies in patients with SLE or other autoimmune diseases. In conclusion, LL-37 is an essential molecule in the pathophysiology of SLE, mainly by its role in increasing the production of IFN by pDCs, which postulates it as a crucial molecule in the pathophysiology of SLE and, given plausibility biology, could serve as a biomarker of the disease.
Study Information
pubmed
2019
2019-12-17T00:00:00.000Z
10.1016/j.jtauto.2019.100029
48
57