Killing Two Birds with One Stone: TNF Antagonists Downregulate Systemic IL-1β in Psoriasis

Contassot, Emmanuel; French, Lars E.

doi:10.1016/j.jid.2020.08.034

Cited by 1 publication

(1 citation statement)

References 11 publications

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“…In mouse models, TNF-α has been shown to regulate the transcription of NLRP3 inflammasome components [91] and exposure to TNF-α results in the significantly increased expression of NLRP3 and pro-IL-1β. The study showed that TNF-α can directly activate NLRP3 inflammasome, without the requirement for a priming signal, and that patients undergoing treatment with TNF-α blocking agents had normalized plasma IL-1β and IL-18 levels, as well as normalized caspase 1 reactivity [92].…”

Section: Inflammasome In Psoriasismentioning

confidence: 97%

Purinergic Signaling and Inflammasome Activation in Psoriasis Pathogenesis

Ferrari

Casciano

Secchiero

et al. 2021

IJMS

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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.

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Section: Inflammasome In Psoriasismentioning

confidence: 97%