ll37 psoriasis LL-37 - LL-37 peptide LL37 LL37 Psoriasis: Unraveling the Role of an Antimicrobial Peptide in Skin Inflammation

LL-37 peptide Psoriasis, a chronic inflammatory skin disease affecting 2-3% of the global population, has long been a subject of intense research. While the exact mechanisms driving its development are complex, emerging evidence points to the significant role of antimicrobial peptides (AMPs), particularly LL37. This article delves into the intricate relationship between LL37 and psoriasis, exploring how this peptide acts as a T-cell autoantigen and contributes to the aberrant immune response characteristic of the disease.

The Multifaceted Nature of LL-37 in Psoriasis Pathogenesis

LL-37, also known as human cationic antimicrobial protein-18 (hCAP18), is a crucial component of the innate immune system.作者：J Fuentes‐Duculan·2017·被引用次数：148—Recently, threepsoriasisautoantigens have been described: cathelicidin (LL37), a disintegrin and metalloprotease domain containing ... It is produced by various cells, including keratinocytes, and plays a vital role in defending the body against microbial infections作者：J Fuentes‐Duculan·2017·被引用次数：148—Recently, threepsoriasisautoantigens have been described: cathelicidin (LL37), a disintegrin and metalloprotease domain containing .... However, in the context of psoriasis, LL37 appears to transition from a protective molecule to a contributor to the disease's autoimmune natureMeasurement of vitamin D and cathelicidin (LL-37) levels ....

Research has established that LL37 is recognized as an autoantigen by a significant portion of psoriasis patients. Studies have shown that circulating T cells in approximately 46% of psoriasis patients, and more frequently in those with moderate-to-severe disease, specifically target LL37. This autoreactivity suggests that the immune system, in its attempt to clear infections or respond to tissue injury, mistakenly identifies LL37 as a foreign threat. This misidentification triggers an inflammatory cascade that perpetuates psoriasis lesions.

One of the key mechanisms through which LL37 contributes to psoriasis pathogenesis is by forming complexes with self-DNA and self-RNAIncreased LL37 in psoriasis and other inflammatory ... - JCI. These complexes are potent activators of the immune system, particularly dendritic cells. When LL37 binds to self-DNA or self-RNA, it can trigger the production of type I interferons (IFN-I) and other pro-inflammatory cytokines. This process is amplified in psoriasis where increased levels of LL37 and extracellular DNA are observed, largely due to the release of neutrophil extracellular traps (NETs). These NETs, composed of self-DNA and proteins including LL37, are characteristic of psoriasis skin and contribute to the Th17 immune response seen in the disease.

Furthermore, LL37 has been shown to induce Toll-like receptor 9 (TLR9) expression in keratinocytes. TLR9 is a receptor that recognizes microbial DNA, but in psoriasis, it becomes aberrantly activated by self-DNA complexed with LL37. This leads to enhanced type I IFN production, further fueling the inflammatory cycle of psoriasis. Oxidative stress and skin injury, common triggers or exacerbating factors in psoriasis, can lead to increased production of LL37 by keratinocytes, initiating or intensifying the immune response.

LL37 and Associated Conditions

The elevated levels of LL37 are not confined to psoriasis alone. Patients with chronic inflammatory disorders, including psoriasis, exhibit an increased risk of cardiovascular disease, and these individuals also tend to have elevated levels of LL37. This suggests a potential link between LL37 and systemic inflammation beyond the skin. Research is ongoing to understand how LL37 might contribute to conditions like atherosclerosis作者：J Lao·2023·被引用次数：17—This study investigated the serum levels ofLL-37and inflammatory cytokines, as well as correlations between them in PsO patients..

Therapeutic Implications and Future Directions

The understanding of LL37's role in psoriasis has opened avenues for novel therapeutic strategies. Topical nanoparticles designed to interfere with the DNA-LL37 complex have shown promise in preclinical studies by disrupting the abnormal immune activation. The peptide LL37 itself is being explored not only for its antimicrobial properties but also for its immunomodulatory effects, suggesting potential as a target for novel therapies for psoriasisEvaluation of HBD-1, HBD-2 and LL-37 levels in patients ....

Targeting the vitamin D pathway has also shown some success in ameliorating psoriasis inflammation, and interestingly, LL37 production is influenced by vitamin D. This highlights a complex interplay of factors contributing to the disease.

In conclusion, LL37 is a critical player in the complex pathogenesis of psoriasisIncreased LL37 in psoriasis and other inflammatory disorders .... Its ability to act as a T-cell autoantigen, its role in forming activating complexes with self-nucleic acids, and its induction of key inflammatory pathways make it a central figure in driving the chronic inflammation characteristic of this skin disease.作者：R Favaro·2024·被引用次数：3—LL37-specific T-cells were detected in up to two-thirds of moderate-to-severepsoriasispatients [7], but whether the presence of specific autoreactive T-cells ... Continued research into the mechanisms of LL37 action holds significant promise for the development of more effective treatments for psoriasis and potentially other autoimmune and inflammatory conditions.