Therapeutic targeting of Toll-like receptors in cutaneous disorders

Matin, Nassim; Tabatabaie, Omidreza; Mohammadinejad, Payam; Rezaei, Nima

doi:10.1517/14728222.2015.1069275

Cited by 7 publications

(5 citation statements)

References 98 publications

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“…TLRs play important roles in linking innate and adaptive immune responses to initiate immediate as well as long-term host defense against danger signals, and dysregulations of TLRs are responsible for the pathogenesis of several inflammatory skin diseases, and therefore, targeting TLRs is of great therapeutic potential to treat skin diseases. Several TLR agonists or antagonists or TLR modulators have been approved or are currently in development to treat skin diseases [105]. We will next review TLR's therapeutic implication, recent advances, and future prospects in treating skin diseases.…”

Section: Tlr-targeted Therapiesmentioning

confidence: 99%

“…Caspofungin (echinocandins), a new class of antifungal drugs, inhibits the synthesis of β -glucan in the fungal cell wall by influencing the interactions between Dectin1 and TLR2, TLR4, or TLR9 [107]. TLR ligands have also been used for the treatment or vaccine development for herpes simplex virus (HSV) [105]. In mice, HSV vaccines adjuvanted with the TLR9 agonist unmethylated CpG are superior to the unadjuvanted vaccine at eliciting a robust HSV-specific cell-mediated immune response [108].…”

Section: Tlr-targeted Therapiesmentioning

confidence: 99%

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The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis

Sun

Liu

Zhang

2019

Journal of Immunology Research

121

105

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As the key defense molecules originally identified in Drosophila, Toll-like receptor (TLR) superfamily members play a fundamental role in detecting invading pathogens or damage and initiating the innate immune system of mammalian cells. The skin, the largest organ of the human body, protects the human body by providing a critical physical and immunological active multilayered barrier against invading pathogens and environmental factors. At the first line of defense, the skin is constantly exposed to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), and TLRs, expressed in a cell type-specific manner by various skin cells, serve as key molecules to recognize PAMPs and DAMPs and to initiate downstream innate immune host responses. While TLR-initiated inflammatory responses are necessary for pathogen clearance and tissue repair, aberrant activation of TLRs will exaggerate T cell-mediated autoimmune activation, leading to unwanted inflammation, and the development of several skin diseases, including psoriasis, atopic dermatitis, systemic lupus erythematosus, diabetic foot ulcers, fibrotic skin diseases, and skin cancers. Together, TLRs are at the interface between innate immunity and adaptive immunity. In this review, we will describe current understanding of the role of TLRs in skin defense and in the pathogenesis of psoriasis and atopic dermatitis, and we will also discuss the development and therapeutic effect of TLR-targeted therapies.

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Section: Tlr-targeted Therapiesmentioning

confidence: 99%

Section: Tlr-targeted Therapiesmentioning

confidence: 99%

The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis

Sun

Liu

Zhang

2019

Journal of Immunology Research

121

105

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“…Infectious agents are plausible environmental triggers for autoimmunity in genetically susceptible individuals. Ongoing studies to identify the triggering environmental antigen in PF will be critically important to make significant progress in the disease's therapy [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Toll-like-Receptor Gene Polymorphisms in Tunisian Endemic Pemphigus Foliaceus

Abida

Bahloul

Elloumi

et al. 2020

BioMed Research International

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Pemphigus foliaceus (PF) is considered to be caused by the combined effects of susceptibility genes and environmental triggers. The polymorphisms of Toll-like receptors (TLRs) genes have been associated with the risk of various autoimmune diseases. The aim of this study was to evaluate the potential association of TLR2-3-4 and 7 gene polymorphisms with Tunisian PF. Fourteen polymorphisms were analyzed in 93 Tunisian PF patients compared to 193 matched healthy controls: rs5743703-rs5743709 and (GT)n repeat (TLR2); rs5743305, rs3775294, and rs3775291 (TLR3), rs4986790 and rs4986791 (TLR4); and rs3853839 (TLR7). Our results showed that the genetic factors varied depending on the epidemiological feature stratification. In fact, in the whole population, no association with the susceptibility to PF was found. The TLR2 GT repeat seems to be closely associated with PF risk in patients originated from the endemic localities (group 3); the GT18 allele and the heterozygous genotype GT18/GT19 seem to confer risk to endemic PF ( P = 0.02 ; OR = 2.3 [1.1-4.9] and P = 0.0002 , OR = 20 [2.5-171], respectively). In contrast, the GT23 repeat could be considered as protector allele ( P = 0.02 , OR = 0.2 [0.06-0.87]). Furthermore, medium GT alleles which induce high promoter activity were also significantly more frequent in patients versus short or long GT repeats ( P = 0.0018 with OR = 3.26 [1.5-7]). On the other hand, the TLR3-rs574305 AA genotype and A allele were significantly more frequent in patients whose age of the onset was above 35 years (group 2) ( P = 0.038 , OR = 1.78 and P = 0.009 , OR = 3.92 , respectively). Besides, the TLR4>rs3775294 A allele was found to be protector only in patients with sporadic features (groups 2 and 4) ( P = 0.03 , OR = 0.57 [0.3-0.9] and P = 0.006 , OR = 0.24 [0.08-0.74], respectively). No statistically significant difference was observed in the genotypic and allelic frequencies of TLR-4 and TLR-7 gene polymorphisms. The present data suggest that TLR2and TLR3 polymorphisms are significantly associated with increased susceptibility to PF in the Tunisian population.

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“…Toll‐like receptors (TLRs) play a key role in recognizing pathogen‐associated molecular patterns, but are also involved in the recognition of damage‐associated molecular patterns . Therefore TLRs control a broad range of biological processes, including inflammatory and immune responses during carcinogenesis. The TLR superfamily contains more than ten different members (TLR 1–13 in humans) .…”

Section: Toll‐like Receptorsmentioning

confidence: 99%

Cancer Immunotherapy: Selected Targets and Small‐Molecule Modulators

Weinmann

2016

ChemMedChem

107

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There is a significant amount of excitement in the scientific community around cancer immunotherapy, as this approach has renewed hope for many cancer patients owing to some recent successes in the clinic. Currently available immuno-oncology therapeutics under clinical development and on the market are mostly biologics (antibodies, proteins, engineered cells, and oncolytic viruses). However, modulation of the immune system with small molecules offers several advantages that may be complementary and potentially synergistic to the use of large biologicals. Therefore, the discovery and development of novel small-molecule modulators is a rapidly growing research area for medicinal chemists working in cancer immunotherapy. This review provides a brief introduction into recent trends related to selected targets and pathways for cancer immunotherapy and their small-molecule pharmacological modulators.

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Therapeutic targeting of Toll-like receptors in cutaneous disorders

Cited by 7 publications

References 98 publications

The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis

The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis

Toll-like-Receptor Gene Polymorphisms in Tunisian Endemic Pemphigus Foliaceus

Cancer Immunotherapy: Selected Targets and Small‐Molecule Modulators

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