ArticleJournal of immunology (Baltimore, Md. : 1950)2018
A Novel Biological Role for Peptidyl-Arginine Deiminases: Citrullination of Cathelicidin LL-37 Controls the Immunostimulatory Potential of Cell-Free DNA.
Article in Journal of immunology (Baltimore, Md. : 1950), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Beyond PAD Inhibition: Emerging Avenues and Natural Products for Targeting Citrullination in Immune Diseases.Biomedicines · 2026Review
- The plasmacytoid dendritic cell paradox in cancer: impaired type I interferon responses in a nucleic acid-rich tumor microenvironment.Frontiers in immunology · 2026Review
- Citrullination of CAMP exacerbating mucosal inflammation in inflammatory bowel disease.Precision clinical medicine · 2025Article
- Antimicrobial Peptides of the Cathelicidin Family: Focus on LL-37 and Its Modifications.International journal of molecular sciences · 2025Review
- LL-37 and citrullinated-LL-37 modulate IL-17A/F-mediated responses and selectively suppress Lipocalin-2 in bronchial epithelial cells.Journal of inflammation (London, England) · 2025Article
- The nature of the post-translational modifications of the autoantigen LL37 influences the autoreactive T-helper cell phenotype in psoriasis.Frontiers in immunology · 2025Article
- Neutrophil-Derived Peptidyl Arginine Deiminase Activity Contributes to Pulmonary Emphysema by Enhancing Elastin Degradation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Between good and evil: Complexation of the human cathelicidin LL-37 with nucleic acids.Biophysical journal · 2024Review
- Citrullination and the protein code: crosstalk between post-translational modifications in cancer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Modulation of innate immunity in airway epithelium for host-directed therapy.Frontiers in immunology · 2023Review
- Immunological investigation of a multiepitope peptide vaccine candidate based on main proteins of SARS-CoV-2 pathogen.PloS one · 2022Article
- The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases.Journal of innate immunity · 2022Review
- TLR2 Activation byFrontiers in immunology · 2022Article
- Upregulating Human Cathelicidin Antimicrobial Peptide LL-37 Expression May Prevent Severe COVID-19 Inflammatory Responses and Reduce Microthrombosis.Frontiers in immunology · 2022Review
- Crosstalk between B cells and neutrophils in rheumatoid arthritis.Immunology · 2021Review
- Proteinous Components of Neutrophil Extracellular Traps Are Arrested by the Cell Wall Proteins ofCells · 2021Article
- Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus.International journal of molecular sciences · 2021Article
- Citrullination-Resistant LL-37 Is a Potent Antimicrobial Agent in the Inflammatory Environment High in Arginine Deiminase Activity.International journal of molecular sciences · 2020Article
- Generation of Monoclonal Antibodies Specific for Native LL37 and Citrullinated LL37 That Discriminate the Two LL37 Forms in the Skin and Circulation of Cutaneous/Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients.Antibodies (Basel, Switzerland) · 2020Article
- Antimicrobial host defence peptides: functions and clinical potential.Nature reviews. Drug discovery · 2020Review
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Authors and funding
14 authors at 6 institutions in 5 countries.
Funding
Abstract
LL-37, the only human cathelicidin that is released during inflammation, is a potent regulator of immune responses by facilitating delivery of oligonucleotides to intracellular TLR-9, thereby enhancing the response of human plasmacytoid dendritic cells (pDCs) to extracellular DNA. Although important for pathogen recognition, this mechanism may facilitate development of autoimmune diseases. In this article, we show that citrullination of LL-37 by peptidyl-arginine deiminases (PADs) hindered peptide-dependent DNA uptake and sensing by pDCs. In contrast, carbamylation of the peptide (homocitrullination of Lys residues) had no effect. The efficiency of LL-37 binding to oligonucleotides and activation of pDCs was found to be inversely proportional to the number of citrullinated residues in the peptide. Similarly, preincubation of carbamylated LL-37 with PAD2 abrogated the peptide's ability to bind DNA. Conversely, LL-37 with Arg residues substituted by homoarginine, which cannot be deiminated, elicited full activity of native LL-37 regardless of PAD2 treatment. Taken together, the data showed that citrullination abolished LL-37 ability to bind DNA and altered the immunomodulatory function of the peptide. Both activities were dependent on the proper distribution of guanidinium side chains in the native peptide sequence. Moreover, our data suggest that cathelicidin/LL-37 is citrullinated by PADs during NET formation, thus affecting the inflammatory potential of NETs. Together this may represent a novel mechanism for preventing the breakdown of immunotolerance, which is dependent on the response of APCs to self-molecules (including cell-free DNA); overactivation may facilitate development of autoimmunity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.