{"doi":"10.3389/fimmu.2025.1621633","title":"Pro-dermcidin and derivatives as potential therapeutics for lethal experimental sepsis","abstract":"A 110-amino acid precursor of dermcidin (pre-dermcidin, pre-DCD) with a 19-residue N-terminal leader signal sequence can be secreted by human eccrine sweat glands as a leader-less pro-domain-containing peptide (pro-DCD), which is enzymatically cleaved to generate C-terminal anti-microbial peptides (dermcidin-1, DCD-1) capable of killing various bacteria. Previously, it was unknown whether pro-DCD could be pharmacologically developed as potential therapeutics for lethal sepsis. Here, we demonstrated that pharmacological suppression of pro-DCD with polyclonal antibodies worsened sepsis-induced inflammation and liver injury, whereas supplementation of pro-DCD or its PEGylation derivatives significantly protected against sepsis, even when given 2-24 h after disease onset. These protective effects were associated with a significant reduction in circulating levels of surrogate biomarkers [e.g., Granulocyte Colony Stimulating Factor (G-CSF), Interleukin-6 (IL-6), keratinocytes-derived chemokine (KC), Monocyte Chemoattractant Protein 1 (MCP-1), Macrophage Inflammatory Protein-2 (MIP-2), and Soluble Tumor Necrosis Factor Receptor I (sTNFRI)], tissue injury, and blood bacterial counts. Although pro-DCD or its PEGylation derivatives failed to directly kill bacteria across a wide range of concentrations, they were able to activate microtubule-associated protein 1A/1B-light chain 3 (LC3), a marker of autophagy and phagosome maturation in LC3-associated bacterial phagocytosis. Our findings suggest that pro-DCD-derived agents hold promise as potential therapies for clinical sepsis.","journal":"Frontiers in Immunology","year":2025,"id":553053,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":565052,"name":"Xiaoling Qiang","orcid":"0000-0001-9176-7407","position":1,"is_corresponding":false},{"id":565053,"name":"Shu Zhu","orcid":"0000-0003-2211-9646","position":2,"is_corresponding":false},{"id":516696,"name":"Jianhua Li","orcid":"0000-0001-5123-485X","position":3,"is_corresponding":false},{"id":1263525,"name":"Lou Li","orcid":null,"position":4,"is_corresponding":false},{"id":247094,"name":"Ping Wang","orcid":"0000-0002-1557-0394","position":5,"is_corresponding":false},{"id":72617,"name":"Kevin J. Tracey","orcid":"0000-0003-1884-6314","position":6,"is_corresponding":false},{"id":109941,"name":"Haichao Wang","orcid":"0000-0002-0211-9000","position":7,"is_corresponding":false},{"id":356765,"name":"Weiqiang Chen","orcid":"0000-0002-8840-1823","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:54:37.527189Z","pmid":"40534887","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}