ArticleInternational journal of molecular sciences2021
Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Discovery of Post-Translationally Modified Epitopes in Autoimmunity: Someone Has to Fish so Everyone Can Eat.Immunological reviews · 2026Review
- Citrullination of CAMP exacerbating mucosal inflammation in inflammatory bowel disease.Precision clinical medicine · 2025Article
- Epigenetic regulatory mechanisms of autoimmune skin diseases: novel biomarkers and therapeutic prospects.Clinical epigenetics · 2025Review
- Antimicrobial Peptides of the Cathelicidin Family: Focus on LL-37 and Its Modifications.International journal of molecular sciences · 2025Review
- Neutrophil extracellular traps in sepsis: trade-off between pros and cons.Burns & trauma · 2025Review
- 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 extracellular traps in homeostasis and disease.Signal transduction and targeted therapy · 2024Review
- New, Old, and Shared Antibody Specificities in Autoimmune Diseases.Antibodies (Basel, Switzerland) · 2024Article
- Synovial microenvironment-influenced mast cells promote the progression of rheumatoid arthritis.Nature communications · 2024Article
- Multi-epitope vaccine design for hepatitis E virus based on protein ORF2 and ORF3.Frontiers in microbiology · 2024Article
- Article
- Proteomic analysis of lysine 2-hydroxyisobutyryl in SLE reveals protein modification alteration in complement and coagulation cascades and platelet activation Pathways.BMC medical genomics · 2023Article
- Could AMPs and B-cells be the missing link in understanding periodontitis?Frontiers in immunology · 2022Article
- Structural aspects of chemical modifications in the MHC-restricted immunopeptidome; Implications for immune recognition.Frontiers in chemistry · 2022Review
- Emerging Roles of Post-Translational Modifications in Skin Diseases: Current Knowledge, Challenges and Future Perspectives.Journal of inflammation research · 2022Review
- Host Defense Peptides: Dual Antimicrobial and Immunomodulatory Action.International journal of molecular sciences · 2021Review
- Centrality of Myeloid-Lineage Phagocytes in Particle-Triggered Inflammation and Autoimmunity.Frontiers in toxicology · 2021Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to "self" nucleic acids, LL37 acts as "danger signal," leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while "fully-citrullinated" LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated "adjuvant-like" properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to "fully citrullinated-LL37," "fully carbamylated-LL37" maintains both innate and adaptive immune-cells' stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.
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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.