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Purinergic Signaling and Inflammasome Activation in Psoriasis Pathogenesis
Psoriasis is a chronic inflammatory disease of the skin associated with systemic and joint manifestations and accompanied by comorbidities, such as metabolic syndrome and increased risk of cardiovascular disease. Psoriasis has a strong genetic basis, but exacerbation requires additional signals that...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430580/ https://www.ncbi.nlm.nih.gov/pubmed/34502368 http://dx.doi.org/10.3390/ijms22179449 |
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author | Ferrari, Davide Casciano, Fabio Secchiero, Paola Reali, Eva |
author_facet | Ferrari, Davide Casciano, Fabio Secchiero, Paola Reali, Eva |
author_sort | Ferrari, Davide |
collection | PubMed |
description | Psoriasis is a chronic inflammatory disease of the skin associated with systemic and joint manifestations and accompanied by comorbidities, such as metabolic syndrome and increased risk of cardiovascular disease. Psoriasis has a strong genetic basis, but exacerbation requires additional signals that are still largely unknown. The clinical manifestations involve the interplay between dendritic and T cells in the dermis to generate a self-sustaining inflammatory loop around the TNFα/IL-23/IL-17 axis that forms the psoriatic plaque. In addition, in recent years, a critical role of keratinocytes in establishing the interplay that leads to psoriatic plaques’ formation has re-emerged. In this review, we analyze the most recent evidence of the role of keratinocytes and danger associates molecular patterns, such as extracellular ATP in the generation of psoriatic skin lesions. Particular attention will be given to purinergic signaling in inflammasome activation and in the initiation of psoriasis. In this phase, keratinocytes’ inflammasome may trigger early inflammatory pathways involving IL-1β production, to elicit the subsequent cascade of events that leads to dendritic and T cell activation. Since psoriasis is likely triggered by skin-damaging events and trauma, we can envisage that intracellular ATP, released by damaged cells, may play a role in triggering the inflammatory response underlying the pathogenesis of the disease by activating the inflammasome. Therefore, purinergic signaling in the skin could represent a new and early step of psoriasis; thus, opening the possibility to target single molecular actors of the purinome to develop new psoriasis treatments. |
format | Online Article Text |
id | pubmed-8430580 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84305802021-09-11 Purinergic Signaling and Inflammasome Activation in Psoriasis Pathogenesis Ferrari, Davide Casciano, Fabio Secchiero, Paola Reali, Eva Int J Mol Sci Review Psoriasis is a chronic inflammatory disease of the skin associated with systemic and joint manifestations and accompanied by comorbidities, such as metabolic syndrome and increased risk of cardiovascular disease. Psoriasis has a strong genetic basis, but exacerbation requires additional signals that are still largely unknown. The clinical manifestations involve the interplay between dendritic and T cells in the dermis to generate a self-sustaining inflammatory loop around the TNFα/IL-23/IL-17 axis that forms the psoriatic plaque. In addition, in recent years, a critical role of keratinocytes in establishing the interplay that leads to psoriatic plaques’ formation has re-emerged. In this review, we analyze the most recent evidence of the role of keratinocytes and danger associates molecular patterns, such as extracellular ATP in the generation of psoriatic skin lesions. Particular attention will be given to purinergic signaling in inflammasome activation and in the initiation of psoriasis. In this phase, keratinocytes’ inflammasome may trigger early inflammatory pathways involving IL-1β production, to elicit the subsequent cascade of events that leads to dendritic and T cell activation. Since psoriasis is likely triggered by skin-damaging events and trauma, we can envisage that intracellular ATP, released by damaged cells, may play a role in triggering the inflammatory response underlying the pathogenesis of the disease by activating the inflammasome. Therefore, purinergic signaling in the skin could represent a new and early step of psoriasis; thus, opening the possibility to target single molecular actors of the purinome to develop new psoriasis treatments. MDPI 2021-08-31 /pmc/articles/PMC8430580/ /pubmed/34502368 http://dx.doi.org/10.3390/ijms22179449 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Ferrari, Davide Casciano, Fabio Secchiero, Paola Reali, Eva Purinergic Signaling and Inflammasome Activation in Psoriasis Pathogenesis |
title | Purinergic Signaling and Inflammasome Activation in Psoriasis Pathogenesis |
title_full | Purinergic Signaling and Inflammasome Activation in Psoriasis Pathogenesis |
title_fullStr | Purinergic Signaling and Inflammasome Activation in Psoriasis Pathogenesis |
title_full_unstemmed | Purinergic Signaling and Inflammasome Activation in Psoriasis Pathogenesis |
title_short | Purinergic Signaling and Inflammasome Activation in Psoriasis Pathogenesis |
title_sort | purinergic signaling and inflammasome activation in psoriasis pathogenesis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430580/ https://www.ncbi.nlm.nih.gov/pubmed/34502368 http://dx.doi.org/10.3390/ijms22179449 |
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