title: Multiple Functions of the New Cytokine-Based Antimicrobial Peptide Thymic Stromal Lymphopoietin (TSLP).
abstract: Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine, hitherto mostly known to be involved in inflammatory responses and immunoregulation. The human tslp gene gives rise to two transcription and translation variants: a long form (lfTSLP) that is induced by inflammation, and a short, constitutively-expressed form (sfTSLP), that appears to be downregulated by inflammation. The TSLP forms can be produced by a number of cell types, including epithelial and dendritic cells (DCs). lfTSLP can activate mast cells, DCs, and T cells through binding to the lfTSLP receptor (TSLPR) and has a pro-inflammatory function. In contrast, sfTSLP inhibits cytokine secretion of DCs, but the receptor mediating this effect is unknown. Our recent studies have demonstrated that both forms of TSLP display potent antimicrobial activity, exceeding that of many other known antimicrobial peptides (AMPs), with sfTSLP having the strongest effect. The AMP activity is primarily mediated by the C-terminal region of the protein and is localized within a 34-mer peptide (MKK34) that spans the C-terminal α-helical region in TSLP. Fluorescent studies of peptide-treated bacteria, electron microscopy, and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of LL-37. Expression of TSLP in skin, oral mucosa, salivary glands, and intestine is part of the defense barrier that aids in the control of both commensal and pathogenic microbes.
authors.affiliation: Department of Oral Biology, Dental Faculty, University of Oslo, PB 1052 Blindern, N-0316 Oslo, Norway. louise.bjerkan@medisin.uio.no.
authors.forename: Louise
authors.initials: L
authors.lastname: Bjerkan
authors.affiliation: Division of Dermatology and Venereology, Department of Clinical Sciences Lund, Lund University, BMC, Tornav&#228;gen 10, SE-22184 Lund, Sweden. andreas.sonesson@med.lu.se.|Dermatology and Venereology, Skane University Hospital, Lasarettsgatan 15, SE-22185 Lund, Sweden. andreas.sonesson@med.lu.se.
authors.forename: Andreas
authors.initials: A
authors.lastname: Sonesson
authors.affiliation: Department of Oral Biology, Dental Faculty, University of Oslo, PB 1052 Blindern, N-0316 Oslo, Norway. karl.schenck@odont.uio.no.
authors.forename: Karl
authors.initials: K
authors.lastname: Schenck
keywords: AMP; TSLP; immunoregulation