Selvakumar Balachandar, Rah Bilal, Jagal Jayalakshmi, Sekar Priyadarshini, Moustafa Raneem, Ramakrishnan Rakhee Kizhuvappat, Haider Mohamed, Ibrahim Saleh Mohamed, Samsudin Rani
Microbiota research group, Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Iron Biology research Group, Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Inflamm Res. 2024 Dec;73(12):2217-2230. doi: 10.1007/s00011-024-01958-6. Epub 2024 Oct 15.
Psoriasis (Ps) is a chronic inflammatory disorder marked by skin plaque formation, driven by immune dysregulation and genetic factors. Despite the available treatments, incidence of Ps is increasing in the dermatology patients. Novel strategies are crucial due to current treatment limitations. The interleukin 17 (IL-17) pathway is pivotal in Ps pathogenesis, however the expression of its putative target gene placenta expressed transcript 1 (Plet1) remains unstudied in Ps. Considering the potential anti-inflammatory properties of N-Acetylglucosamine (GlcNAc), our study explored its role in modulating Plet1 expression in an imiquimod (IMQ)-induced Ps mouse model. Our data demonstarted a significant reduction of inflammation and Psoriasis Area and Severity Index (PASI) scores, downregulation of growth factors (GFs), IL-17 A, and MAPK expression after GlcNAc treatment. In addition, GlcNAc treatment reduced neutrophils, monocyte-dendritic cells (Mo-DC) and conventional T cells (Tcons) while increasing monocyte-macrophages (Mo-Macs) and regulatory T cells (Tregs). GlcNAc treatment also downregulated Plet1 overexpression in psoriatic mouse skin and in vitro, reduced proliferation and apoptosis in IL-17 A stimulated human dermal fibroblasts (HDF), along with IL-17 A and TGF-β mRNA expression. Together, these data suggest that, GlcNAc interferes with downstream mechanisms in IL-17 pathway and downregulating Plet1 expression, presenting a promising strategy for Ps treatment.
银屑病（Ps）是一种慢性炎症性疾病，其特征为皮肤斑块形成，由免疫失调和遗传因素驱动。尽管有可用的治疗方法，但在皮肤科患者中，Ps的发病率仍在上升。由于当前治疗存在局限性，新策略至关重要。白细胞介素17（IL-17）通路在Ps发病机制中起关键作用，然而其假定的靶基因胎盘表达转录本1（Plet1）在Ps中的表达尚未得到研究。考虑到N-乙酰葡糖胺（GlcNAc）的潜在抗炎特性，我们的研究在咪喹莫特（IMQ）诱导的Ps小鼠模型中探讨了其在调节Plet1表达中的作用。我们的数据表明，GlcNAc治疗后炎症和银屑病面积及严重程度指数（PASI）评分显著降低，生长因子（GFs）、IL-17 A和丝裂原活化蛋白激酶（MAPK）表达下调。此外，GlcNAc治疗减少了中性粒细胞、单核细胞-树突状细胞（Mo-DC）和常规T细胞（Tcons），同时增加了单核细胞-巨噬细胞（Mo-Macs）和调节性T细胞（Tregs）。GlcNAc治疗还下调了银屑病小鼠皮肤和体外Plet1的过表达，降低了IL-17 A刺激的人皮肤成纤维细胞（HDF）的增殖和凋亡，以及IL-17 A和转化生长因子-β（TGF-β）mRNA表达。总之，这些数据表明，GlcNAc干扰IL-17通路的下游机制并下调Plet1表达，为Ps治疗提供了一种有前景的策略。
