Kumar Vijay
Children Health Clinical Unit, Faculty of Medicine and Biomedical Sciences, Mater Research, University of Queensland, ST Lucia, Brisbane, Queensland 4078, Australia.
School of Biomedical Sciences, Faculty of Medicine, University of Queensland, ST Lucia, Brisbane, Queensland 4078, Australia.
EXCLI J. 2021 Jan 7;20:52-79. doi: 10.17179/excli2020-3114. eCollection 2021.
The Indian Ayurvedic physicians knew the concept of inflammation dating back to 1500 BC. The continuous progress in the immunology of inflammation has explained its undiscovered mechanisms. For example, the discovery of Toll-like receptor 4 (TLR4) in humans (1997) has revolutionized the field of infection biology and innate immunity. The laboratory mice have shown twelve TLRs and express TLR10 (CD290) as a disrupted pseudogene, and humans have ten functional TLRs. Now, it is well established that TLRs play a significant role in different infectious and inflammatory diseases. Skin inflammation and other associated inflammatory diseases, including atopic dermatitis (AD), acne vulgaris, and psoriasis, along with many skin cancers are major health problems all over the world. The continuous development in the immunopathogenesis of inflammatory skin diseases has opened the window of opportunity for TLRs in studying their role. Hence, the manuscript explores the role of different TLRs in the pathogenesis of skin inflammation and associated inflammatory diseases. The article starts with the concept of inflammation, its origin, and the impact of TLRs discovery on infection and inflammation biology. The subsequent section describes the burden of skin-associated inflammatory diseases worldwide and the effect of the geographical habitat of people affecting it. The third section explains skin as an immune organ and explains the expression of different TLRs on different skin cells, including keratinocytes, Langerhans cells (LCs), skin fibroblasts, and melanocytes. The fourth section describes the impact of TLRs on these cells in different skin-inflammatory conditions, including acne vulgaris, AD, psoriasis, and skin cancers. The article also discusses the use of different TLR-based therapeutic approaches as specific to these inflammatory skin diseases.
印度阿育吠陀医生早在公元前1500年就知晓炎症的概念。炎症免疫学的不断发展解释了其尚未被发现的机制。例如,人类Toll样受体4(TLR4)的发现(1997年)给感染生物学和固有免疫领域带来了变革。实验室小鼠显示有12种TLR,并将TLR10(CD290)作为一个失活的假基因来表达,而人类有10种功能性TLR。如今,人们已经充分认识到TLR在不同的感染性和炎症性疾病中发挥着重要作用。皮肤炎症以及其他相关炎症性疾病,包括特应性皮炎(AD)、寻常痤疮和银屑病,连同许多皮肤癌,都是世界各地的主要健康问题。炎症性皮肤病免疫发病机制的不断发展为研究TLR在其中的作用打开了机遇之窗。因此,本手稿探讨了不同TLR在皮肤炎症及相关炎症性疾病发病机制中的作用。文章开篇介绍了炎症的概念、其起源以及TLR的发现对感染和炎症生物学的影响。随后的部分描述了全球与皮肤相关的炎症性疾病的负担以及人们的地理栖息地对其产生的影响。第三部分将皮肤解释为一个免疫器官,并阐述了不同TLR在不同皮肤细胞上的表达,这些细胞包括角质形成细胞、朗格汉斯细胞(LCs)、皮肤成纤维细胞和黑素细胞。第四部分描述了在不同的皮肤炎症状态下,包括寻常痤疮、AD、银屑病和皮肤癌,TLR对这些细胞的影响。文章还讨论了针对这些炎症性皮肤病使用基于不同TLR的治疗方法。