title: The tripeptide KdPT ameliorates ongoing psoriasis-like skin inflammation in murine and human skin.
abstract: Psoriasis is a chronic inflammatory disease appearing as scaly erythematous cutaneous lesions, which are characterized by parakeratosis and acanthosis as well as the infiltration of immune cells, such as T helper-1 and T helper-17 cells. Here, we demonstrated that KdPT, a tripeptide structurally related to the C-terminal amino acids of alpha-melanocyte-stimulating hormone, which was previously shown to exhibit anti-inflammatory effects in intestinal inflammation, ameliorated ongoing disease in the mouse model of imiquimod-induced psoriasis-like skin inflammation and in the small xenotransplant mouse model of psoriasis. We could show that systemic KdPT treatment significantly reduced hyperkeratosis and acanthosis in murine as well as human skin. Moreover, KdPT upregulated Foxp3 in CD4+T cells from mice and from peripheral blood of individuals with psoriasis and decreased the expression of type 1 inflammatory cytokines, indicating that the beneficial effect of KdPT was, at least in part, mediated by the induction of functional regulatory T cells that suppressed the activation of pathogenic CD4+IFN-γ+and CD4+IL-17+T cells. Thus, these data might suggest KdPT as a potential novel therapeutic alternative for the treatment of psoriasis.
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.|Cells in Motion - Cluster of Excellence, University of Münster, Münster, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Mykicki
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.|CRC1009 Breaking Barriers, University of Münster, Münster, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Klenner
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.|Interdisciplinary Center of Clinical Research (IZKF), University of Münster, Münster, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Baumann
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: Matteo
authors.initials: M
authors.lastname: Auriemma
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Sternemann
authors.affiliation: Dr. August Wolff GmbH & Co. KG Arzneimittel, Bielefeld, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Soeberdt
authors.affiliation: Erasmus University Rotterdam, Rotterdam, The Netherlands.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Elliott
authors.affiliation: Dr. August Wolff GmbH & Co. KG Arzneimittel, Bielefeld, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Abels
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.|Cells in Motion - Cluster of Excellence, University of Münster, Münster, Germany.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Luger
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.|Cells in Motion - Cluster of Excellence, University of Münster, Münster, Germany.|CRC1009 Breaking Barriers, University of Münster, Münster, Germany.|Interdisciplinary Center of Clinical Research (IZKF), University of Münster, Münster, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Loser
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007642:Keratosis / Q000188:drug therapy; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D000893:Anti-Inflammatory Agents; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C000611649:IFNG protein, mouse; D020381:Interleukin-17; C568397:KdPT tripeptide; D009842:Oligopeptides; D007371:Interferon-gamma
keywords: Th1 and Th17 cells; psoriasis; regulatory T cells; tolerogenic dendritic cells