Toll-Like Receptors: Role in Dermatological Disease

Hari, Aswin; Flach, Tracy L.; Shi, Yan; Mydlarski, P. Régine

doi:10.1155/2010/437246

Cited by 92 publications

(104 citation statements)

References 186 publications

(218 reference statements)

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“…In contrast, DDCs express TLRs recognizing both bacteria and viruses (8). So far, the ability of TLR agonists to stimulate cutaneous DCs has mostly been tested in vitro (9). However, other skin-resident cells such as keratinocytes, melanocytes, endothelial cells, and fibroblasts also express TLRs and can release cytokines that contribute to DC maturation and the induction and skewing of T cells (10,11).…”

mentioning

confidence: 99%

Intradermal Delivery of TLR Agonists in a Human Explant Skin Model: Preferential Activation of Migratory Dendritic Cells by Polyribosinic-Polyribocytidylic Acid and Peptidoglycans

Oosterhoff

Heusinkveld

Lougheed

et al. 2013

The Journal of Immunology

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TLR agonists are attractive candidate adjuvants for therapeutic cancer vaccines as they can induce a balanced humoral and T cell–mediated immune response. With a dense network of dendritic cells (DCs) and draining lymphatics, the skin provides an ideal portal for vaccine delivery. Beside direct DC activation, TLR agonists may also induce DC activation through triggering the release of inflammatory mediators by accessory cells in the skin microenvironment. Therefore, a human skin explant model was used to explore the in vivo potential of intradermally delivered TLR agonists to stimulate Langerhans cells and dermal DCs in their natural complex tissue environment. The skin-emigrated DCs were phenotyped and analyzed for T cell stimulatory capacity. We report that, of six tested TLR-agonists, the TLR2 and -3 agonists peptidoglycan (PGN) and polyribosinic-polyribocytidylic acid (Poly I:C) were uniquely able to enhance the T cell–priming ability of skin-emigrated DCs, which, in the case of PGN, was accompanied by Th1 polarization. The enhanced priming capacity of Poly I:C–stimulated DCs was associated with a strong upregulation of appropriate costimulatory molecules, including CD70, whereas that of PGN-stimulated DCs was associated with the release of a broad array of proinflammatory cytokines. Transcriptional profiling further supported the notion that the PGN- and Poly I:C–induced effects were mediated through binding to TLR2/nucleotide-binding oligomerization domain 2 and TLR3/MDA5, respectively. These data warrant further exploration of PGN and Poly I:C, alone or in combination, as DC-targeted adjuvants for intradermal cancer vaccines.

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mentioning

confidence: 99%

Intradermal Delivery of TLR Agonists in a Human Explant Skin Model: Preferential Activation of Migratory Dendritic Cells by Polyribosinic-Polyribocytidylic Acid and Peptidoglycans

Oosterhoff

Heusinkveld

Lougheed

et al. 2013

The Journal of Immunology

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“…TLR downstream signalling pathways have been implicated in autoimmune diseases like psoriasis [6,11,12]. Toll-like receptor 9 (TLR9) singlenucleotide polymorphism (SNP) rs187084 was found to affect response to NB-UVB.…”

Section: Photochemotherapymentioning

confidence: 99%

Genetic Influences on Pharmacological Interventions in Psoriasis

Ahmed¹,

Yusuf²

2017

J Clin Exp Dermatol Res

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Psoriasis is a common chronic inflammatory disease that affects 2% of the population. Therapeutic intervention for psoriasis mainly targets inflammatory cascade through the use of topical agents, phototherapy, systemic agents and the newer biologic agents. The efficacy of many treatments used in psoriasis varies from patient to patient, and some of this variance in response can presumably be attributed to genetic differences. While current research findings are still limited, the clinical utilization of pharmacogenetics allows for tailored treatment plans that have the potential for better response amongst patients as well as conserving expenditures and healthcare resources. In this review, we hope to focus and summarize the conclusions and findings of studies done on the topic of pharmacogenetics in the treatment of psoriasis.

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“…Atopowe zapalenie skóry (AZS) jest przewlekłą dermatozą zapalną, która dotyczy około 20% popu lacji dziecięcej [55]. U chorych na AZS występuje zwiększona skłonność do rozwoju infekcji bateryjnych (S. aureus), grzybiczych (Malassezia sp., C. albicans) i wirusowych (HSV) spowodowana redukcją syntezy peptydów przeciwbakteryjnych, zmniejszoną rekrutacją komórek odporności wrodzonej: PMN, pDC i NK, oraz uszkodzeniem bariery naskórkowej [56,57].…”

Section: Choroby Alergiczne Skóryunclassified

“…Nikiel, stanowiący najczęstszą przyczynę alergicznego wyprysku kontaktowego, może powodować aktywację receptorów TLR4 u ludzi i myszy [55,62,63]. Najnowsze badania wykazały również zdolność wiązania TLR4 przez kobalt i pallad [64].…”

Section: Choroby Alergiczne Skóryunclassified

The role of Toll-like receptors in skin diseases

Bacharewicz¹,

Reduta²,

Flisiak³

2014

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StreSzczenieUkład odpornościowy wrodzony ma zdolność rozpoznawania drobnoustrojów za pośrednictwem obecnych na powierzchni komórek przez błonowych glikoprotein określanych jako receptory Tolllike (ang. Toll-like receptors -TLR). Receptory te, obecne na komórkach układu immunologicznego: makrofagach, komórkach dendrytycznych, mastocytach i określonych subpopulacjach limfocytów, pełnią ważną funkcję obronną w zakażeniach bakteryjnych, wirusowych i grzybiczych. Połą-czenie TLR z fragmentem drobnoustroju określanym jako wzorzec molekularny związany z patogenem (ang. pathogen-associated molecular pattern -PAMP) inicjuje wewnątrzkomórkowe mechanizmy prowadzące do wytwarzania cytokin prozapalnych. W zależności od rozpoznawanych ligandów TLR są klasyfikowane na podrodziny. Dotychczas opisano 13 różnych TLR u myszy i 11 u ludzi, które podzielono na TLR zewnątrzkomórkowe: TLR 1, 2, 4, 5, 6, 10, 11 oraz wewnątrzkomórko-we, zlokalizowane w endosomach: TLR 3, 7, 8, 9. Badania ostatnich lat wskazują również na ich rolę w rozwoju szeregu chorób, w tym wielu dermatoz. Występowanie TLR stwierdzono na powierzchni komórek naskórka i skóry właściwej, m.in. na keratynocytach, komórkach Langerhansa, fibroblastach, komórkach śródbłonka naczyń, a nawet na melanocytach i adipocytach. W pracy przedstawiono budowę i funkcję TLR oraz ich udział w patogenezie wybranych chorób skóry -infekcyjnych: bakteryjnych, wirusowych i grzybiczych, a także autoimmunologicznych, alergicznych oraz nowotworowych. Dokładne poznanie roli tych receptorów w rozwoju poszczególnych chorób stwarza możliwość ich wykorzystania w leczeniu schorzeń dermatologicznych. AbStrActThe innate immune system has the ability to recognize pathogens through Tolllike receptors (TLRs), which are transmembrane glycoproteins on the cell surface. These receptors present on the surface of immunological cells -macrophages, dendritic cells, mast cells and some populations of lymphocytes -play an important role in the defense against bacterial, viral and fungal infections. The connection of a Tolllike receptor with the microbial cell component known as pathogen associated molecular pattern (PAMP) induces intracellular mechanisms leading to the synthesis of proinflammatory cytokines. Depending on the kind of the recognized ligand, TLRs are classified into subfamilies. So far, 13 TLRs have been described in mice and 11 in humans. These receptors may be expressed extracellularly (TLRs 1, 2, 4, 5, 6, 10, 11) or intracellularly, located in endosomes (TLRs 3,7,8,9). Recent studies rola receptorów toll-like w chorobach skóry the role of toll-like receptors in skin diseases Joanna bacharewicz, teresa reduta, iwona Flisiak

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Toll-Like Receptors: Role in Dermatological Disease

Cited by 92 publications

References 186 publications

Intradermal Delivery of TLR Agonists in a Human Explant Skin Model: Preferential Activation of Migratory Dendritic Cells by Polyribosinic-Polyribocytidylic Acid and Peptidoglycans

Intradermal Delivery of TLR Agonists in a Human Explant Skin Model: Preferential Activation of Migratory Dendritic Cells by Polyribosinic-Polyribocytidylic Acid and Peptidoglycans

Genetic Influences on Pharmacological Interventions in Psoriasis

The role of Toll-like receptors in skin diseases

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