Toll-like receptors in atopic dermatitis: pathogenesis and therapeutic implications
Toll-like receptors (TLR), the key players of the innate immune system, contribute to the pathogenesis of atopic dermatitis (AD) through multiple pathways. TLRs play a crucial role in delaying barrier repair, promoting Th2-mediated dermatitis, shifting the response toward Th1 in the chronic phase, a...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844025006061 |
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| author | Ahmad Vafaeian Fateme Rajabi Nima Rezaei |
| author_facet | Ahmad Vafaeian Fateme Rajabi Nima Rezaei |
| author_sort | Ahmad Vafaeian |
| collection | DOAJ |
| description | Toll-like receptors (TLR), the key players of the innate immune system, contribute to the pathogenesis of atopic dermatitis (AD) through multiple pathways. TLRs play a crucial role in delaying barrier repair, promoting Th2-mediated dermatitis, shifting the response toward Th1 in the chronic phase, and contributing to the establishment of the itch-scratch cycle, as well as mediating the effects of UV radiation. The dysregulation of proinflammatory and immunomodulatory effects of TLRs can be attributed to their ligand structures, receptor heterodimerization, the relative frequency of each TLR, interactions with other receptors/signalling pathways, cytokine milieu, and genetic polymorphisms. Current AD treatments like vitamin-D analogs, tacrolimus, and cyclosporine partially work through TLR modulation. Direct TLR stimulation using different compounds has shown therapeutic benefits in preclinical studies. However, significant challenges exist, including off-target effects due to ubiquitous TLR expression and complex roles in immune responses. Future directions include CRISPR-based gene editing to understand TLR functions, development of specific TLR modulators for targeted therapy, and machine learning applications to predict drug responses and identify novel ligands. Patient heterogeneity, including the presence or absence of polymorphisms, variations in TLR expression levels, and differences in immune responses, underscores the need for personalized therapeutic approaches. |
| format | Article |
| id | doaj-art-b4427e81b78d4c0d894314ae4491d43e |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-b4427e81b78d4c0d894314ae4491d43e2025-02-09T05:00:39ZengElsevierHeliyon2405-84402025-02-01113e42226Toll-like receptors in atopic dermatitis: pathogenesis and therapeutic implicationsAhmad Vafaeian0Fateme Rajabi1Nima Rezaei2Universal Scientific Education and Research Network (USERN), Tehran, Iran; Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, IranUniversal Scientific Education and Research Network (USERN), Tehran, Iran; Center for Research & Training in Skin Diseases & Leprosy, Tehran University of Medical Sciences, Tehran, IranUniversal Scientific Education and Research Network (USERN), Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Sheffield, UK; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Corresponding author. Universal Scientific Education and Research Network (USERN), Tehran, Iran.Toll-like receptors (TLR), the key players of the innate immune system, contribute to the pathogenesis of atopic dermatitis (AD) through multiple pathways. TLRs play a crucial role in delaying barrier repair, promoting Th2-mediated dermatitis, shifting the response toward Th1 in the chronic phase, and contributing to the establishment of the itch-scratch cycle, as well as mediating the effects of UV radiation. The dysregulation of proinflammatory and immunomodulatory effects of TLRs can be attributed to their ligand structures, receptor heterodimerization, the relative frequency of each TLR, interactions with other receptors/signalling pathways, cytokine milieu, and genetic polymorphisms. Current AD treatments like vitamin-D analogs, tacrolimus, and cyclosporine partially work through TLR modulation. Direct TLR stimulation using different compounds has shown therapeutic benefits in preclinical studies. However, significant challenges exist, including off-target effects due to ubiquitous TLR expression and complex roles in immune responses. Future directions include CRISPR-based gene editing to understand TLR functions, development of specific TLR modulators for targeted therapy, and machine learning applications to predict drug responses and identify novel ligands. Patient heterogeneity, including the presence or absence of polymorphisms, variations in TLR expression levels, and differences in immune responses, underscores the need for personalized therapeutic approaches.http://www.sciencedirect.com/science/article/pii/S2405844025006061Atopic dermatitisItchPathogenesisToll-like receptorsInnate immunity |
| spellingShingle | Ahmad Vafaeian Fateme Rajabi Nima Rezaei Toll-like receptors in atopic dermatitis: pathogenesis and therapeutic implications Heliyon Atopic dermatitis Itch Pathogenesis Toll-like receptors Innate immunity |
| title | Toll-like receptors in atopic dermatitis: pathogenesis and therapeutic implications |
| title_full | Toll-like receptors in atopic dermatitis: pathogenesis and therapeutic implications |
| title_fullStr | Toll-like receptors in atopic dermatitis: pathogenesis and therapeutic implications |
| title_full_unstemmed | Toll-like receptors in atopic dermatitis: pathogenesis and therapeutic implications |
| title_short | Toll-like receptors in atopic dermatitis: pathogenesis and therapeutic implications |
| title_sort | toll like receptors in atopic dermatitis pathogenesis and therapeutic implications |
| topic | Atopic dermatitis Itch Pathogenesis Toll-like receptors Innate immunity |
| url | http://www.sciencedirect.com/science/article/pii/S2405844025006061 |
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