Mykicki Nadine, Klenner Lars, Baumann Christoph, Auriemma Matteo, Sternemann Carlo, Soeberdt Michael, Elliott Graham R, Abels Christoph, Luger Thomas A, Loser Karin
Department of Dermatology, University of Münster, Münster, Germany.
Cells in Motion - Cluster of Excellence, University of Münster, Münster, Germany.
Exp Dermatol. 2017 Apr;26(4):328-334. doi: 10.1111/exd.13145. Epub 2016 Dec 9.
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.
银屑病是一种慢性炎症性疾病，表现为鳞屑性红斑皮肤损害，其特征为角化不全和棘层肥厚以及免疫细胞浸润，如辅助性T细胞1型和辅助性T细胞17型细胞。在此，我们证明了KdPT，一种与α-黑素细胞刺激素C末端氨基酸结构相关的三肽，此前已证明其在肠道炎症中具有抗炎作用，可改善咪喹莫特诱导的银屑病样皮肤炎症小鼠模型和银屑病小型异种移植小鼠模型中的现有疾病。我们可以证明，全身性KdPT治疗可显著减轻小鼠和人类皮肤中的角化过度和棘层肥厚。此外，KdPT上调了来自小鼠以及银屑病患者外周血的CD4 T细胞中的Foxp3，并降低了1型炎性细胞因子的表达，表明KdPT的有益作用至少部分是由诱导功能性调节性T细胞介导的，这些调节性T细胞抑制了致病性CD4 IFN-γ和CD4 IL-17 T细胞的活化。因此，这些数据可能表明KdPT是治疗银屑病的一种潜在新型治疗选择。
