title: Cathelicidin LL-37: a defense molecule with a potential role in psoriasis pathogenesis.
abstract: Epidermal keratinocytes produce and secrete antimicrobial peptides (AMPs) that subsequently form a chemical shield on the skin surface. Cathelicidins are one family of AMPs in skin with various further immune functions. Consequently, dysfunction of these peptides has been implicated in the pathogenesis of inflammatory skin disease. In particular, the cathelicidin LL-37 is overexpressed in inflamed skin in psoriasis, binds to extracellular self-DNA released from dying cells and converts self-DNA in a potent stimulus for plasmacytoid dendritic cells (pDCs). Subsequently, pDCs secrete type I interferons and trigger an auto-inflammatory cascade. Paradoxically, therapies targeting the vitamin D pathway such as vitamin D analogues or UVB phototherapy ameliorate cutaneous inflammation in psoriasis but strongly induce cathelicidin expression in skin at the same time. Current evidence now suggests that self-DNA present in the cytosol of keratinocytes is also pro-inflammatory active and triggers IL-1β secretion in psoriatic lesions through the AIM2 inflammasome. This time, however, binding of LL-37 to self-DNA neutralizes DNA-mediated inflammation. Hence, cathelicidin LL-37 shows contrasting roles in skin inflammation in psoriasis and might serve as a target for novel therapies for this chronic skin disease.
authors.affiliation: Department of Dermatology and Allergy, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Dombrowski
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schauber
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000502:physiology*; D004247:DNA / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D058847:Inflammasomes / Q000502:physiology; D015603:Keratinocytes / Q000473:pathology / Q000502:physiology; D011565:Psoriasis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D014807:Vitamin D / Q000502:physiology; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D058847:Inflammasomes; D014807:Vitamin D; D004247:DNA; D054804:Cathelicidins