{"entity": "publication", "iuid": "e0c3f1f132c34ee19f8fcd6d759bc80e", "timestamp": "2026-10-01T11:58:01.276Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e0c3f1f132c34ee19f8fcd6d759bc80e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e0c3f1f132c34ee19f8fcd6d759bc80e"}}, "title": "The di-leucine motif in the host defense peptide LL-37 is essential for initiation of autophagy in human macrophages.", "authors": [{"family": "Rekha", "given": "Rokeya Sultana", "initials": "RS"}, {"family": "Padhi", "given": "Avinash", "initials": "A"}, {"family": "Frengen", "given": "Nicolai", "initials": "N"}, {"family": "Hauenstein", "given": "Julia", "initials": "J"}, {"family": "V\u00e9gv\u00e1ri", "given": "\u00c1kos", "initials": "\u00c1"}, {"family": "Agerberth", "given": "Birgitta", "initials": "B"}, {"family": "M\u00e5nsson", "given": "Robert", "initials": "R"}, {"family": "Gu\u00f0mundsson", "given": "Gu\u00f0mundur H", "initials": "GH"}, {"family": "Bergman", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2025-01-28", "journal": {"title": "Cell Reports", "issn": "2211-1247", "volume": "44", "issue": "1", "pages": "115031", "issn-l": null}, "abstract": "The human cathelicidin peptide LL-37 induces autophagy in human macrophages. Different post-translational modifications (PTMs) such as citrullination, acetylation, and formylation impact LL-37, yet their effect on autophagy remains unknown. Thus, we set out to study how the cellular source could impact PTM of LL-37 and subsequent effects on autophagy initiation. Neutrophil-released LL-37 failed to induce autophagy, unlike macrophage-released LL-37. Mass spectrometry analysis revealed modifications on neutrophil-derived LL-37, especially at the N terminus, while macrophage-derived LL-37 remained mostly native. Native LL-37 initiated autophagy, while formylated and acetylated versions did not. Truncated peptides lacking the N-terminal di-leucine motif or substituted with di-alanine did not initiate autophagy. Native LL-37 failed to initiate autophagy in macrophages with genetic inactivation of dipeptidyl peptidase-1. An intact N-terminal di-leucine motif in LL-37 was crucial for autophagy initiation, and modifications abrogated the effects. This pathway presents a novel way to regulate the effects of LL-37 in infection or inflammation.", "doi": "10.1016/j.celrep.2024.115031", "pmid": "39708316", "labels": [], "xrefs": [{"db": "pii", "key": "S2211-1247(24)01382-2"}], "notes": [], "created": "2026-10-01T08:28:03.173Z", "modified": "2026-10-01T08:28:03.202Z"}