Toll-like receptors (TLRs) are a class of conserved receptors that recognize pathogen-associated molecular patterns (PAMPs) present in microbes. In humans, at least ten TLRs have been identified, and their recognition targets range from bacterial endotoxins to lipopeptides, DNA, dsRNA, ssRNA, fungal products, and several host factors. Of dermatological interest, these receptors are expressed on several skin cells including keratinocytes, melanocytes, and Langerhans cells. TLRs are essential in identifying microbial products and are known to link the innate and adaptive immune systems. Over the years, there have been significant advances in our understanding of TLRs in skin inflammation, cutaneous malignancies, and defence mechanisms. In this paper, we will describe the association between TLRs and various skin pathologies and discuss proposed TLR therapeutics.

Introduction Corynebacterium tuberculostearicum (C. t.) is a ubiquitous bacterium that colonizes human skin. In contrast to other members of the genus Corynebacterium, such as toxigenic Corynebacterium diphtheriae or the opportunistic pathogen Corynebacterium jeikeium, several studies suggest that C. t. may play a role in skin health and disease. However, the mechanisms underlying these effects remain poorly understood. Methods To investigate whether C. t. induces inflammatory pathways in primary human epidermal keratinocytes (HEKs) and human cutaneous squamous carcinoma cells (SCCs), cell culture, reverse transcription‐polymerase chain reaction (PCR), enzyme‐linked immunosorbent assay, immunofluorescence microscopy, Western blot, chromatin immunoprecipitation‐PCR, small interfering RNA knockdown and luciferase reporter expression system were used. Results Herein, we demonstrate that C. t. upregulates the messenger RNA (mRNA) and protein levels of inflammatory mediators in two human skin cell lines, HEKs and SCCs. We further show activation of the canonical nuclear factor‐κB (NF‐κB) pathway in response to C. t. infection, including phosphorylation of the inhibitor of κB (IκB), the nuclear translocation of NF‐κB subunit (NF‐κB‐P65) and the recruitment of NF‐κB‐P65 and RNA polymerase to the NF‐κB response elements at the promoter region of the inflammatory genes. Lastly, the data confirm that C. t.‐induced tumor necrosis factor mRNA expression in HEKs is toll‐like receptor 2 (TLR2) dependent. Conclusion Our results offer a mechanistic model for C. t.‐induced inflammation in human keratinocytes via TLR2 and activation of IκB kinase and downstream signaling through the canonical NF‐κB pathway. Relevance to chronic inflammatory diseases of the skin and cutaneous oncology is discussed.

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The specialty of dermatology is constantly changing to meet the medical needs of our society. The discipline is in flux because of a variety of factors such as growing population needs, technological advancements, fiscal restraint, and demographic changes. As part of an in-depth review of the specialty, the Dermatology Working Group (DWG) for the Royal College of Physicians and Surgeons of Canada sought to determine whether the current training configuration is suitably preparing graduates to meet the societal health needs of dermatology patients. In this first of a 2-part series, the authors conducted comprehensive literature and historical reviews and a jurisdictional analysis to understand the current state of dermatology practice in Canada. Herein, they explore trends in the dermatology workforce, population needs, accessibility, and wait times, as well as issues in undergraduate and postgraduate medical education. In a subsequent publication, the DWG will utilize information gained from this historical analysis and jurisdictional review, stakeholder perspectives, and a national survey to shape the future of dermatology training in Canada.

Although preliminary data suggest that IVIG is a safe and effective therapy for many skin disorders, uncontrolled clinical trials, case series, and anecdotal case reports dominate the literature. Collaborative randomized controlled trials are required to firmly establish the role of IVIG in dermatology.