Exploring the Role of IL-36 Cytokines as a New Target in Psoriatic Disease

Iznardo, Helena; Puig, L.

doi:10.3390/ijms22094344

Cited by 49 publications

(41 citation statements)

References 58 publications

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“…IL-36 cytokines are expressed in various cell types, including keratinocytes and immune cells [ 58 , 59 ], and are abundantly present in the skin [ 60 ]. They are released as a precursor and require processing by specific proteases, especially derived from neutrophils, to become bioactive [ 61 , 62 , 63 , 64 ]. IL-36α, -β, and -γ through the IL-36 receptor (IL-36R) activate nuclear factor-κB (NF-κB) and mitogen activated protein kinase (MAPK), thus inducing the activation of downstream pathways responsible for the production of pro-inflammatory cytokines, chemokines and costimulatory molecules.…”

Section: Pathogenesismentioning

confidence: 99%

Pustular Psoriasis: From Pathophysiology to Treatment

Genovese

Moltrasio

Cassano³

et al. 2021

Biomedicines

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Pustular psoriasis (PP) is a clinicopathological entity encompassing different variants, i.e., acute generalized PP (GPP), PP of pregnancy (impetigo herpetiformis), annular (and circinate) PP, infantile/juvenile PP, palmoplantar PP/palmoplantar pustulosis, and acrodermatitis continua of Hallopeau (ACH), which have in common an eruption of superficial sterile pustules on an erythematous base. Unlike psoriasis vulgaris, in which a key role is played by the adaptive immune system and interleukin (IL)-17/IL-23 axis, PP seems to be characterized by an intense inflammatory response resulting from innate immunity hyperactivation, with prominent involvement of the IL-36 axis. Some nosological aspects of PP are still controversial and debated. Moreover, owing to the rarity and heterogeneity of PP forms, data on prognosis and therapeutic management are limited. Recent progresses in the identification of genetic mutations and immunological mechanisms have promoted a better understanding of PP pathogenesis and might have important consequences on diagnostic refinement and treatment. In this narrative review, current findings in the pathogenesis, classification, clinical features, and therapeutic management of PP are briefly discussed.

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Section: Pathogenesismentioning

confidence: 99%

Pustular Psoriasis: From Pathophysiology to Treatment

Genovese

Moltrasio

Cassano³

et al. 2021

Biomedicines

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“…Most recently, administration of the monoclonal antibody “Spesolimab” (BI-655130) significantly improved GPP patient outcomes by targeting IL-36R. In phase I clinical trials, BI-655130 administration drastically improved GPP patient’s skin symptoms by 80% [ 55 ], with Spesolimab also showing positive effects in phase II trials for palmoplantar pustulosis [ 56 ]. In addition to directly targeting the IL-36R, there is evidence emerging that the upstream activators of IL-36 cytokines, namely the proteases Cathepsin G and elastase, also represent possible therapeutic targets for this disease.…”

Section: The Role Of Il-36 In the Pathogenesis Of Inflammatory Diseasesmentioning

confidence: 99%

IL-36 cytokines in inflammatory and malignant diseases: not the new kid on the block anymore

Byrne

Baker

Houston

et al. 2021

Cell. Mol. Life Sci.

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The IL-36 family of cytokines were first identified in 2000 based on their sequence homology to IL-1 cytokines. Over subsequent years, the ability of these cytokines to either agonise or antagonise an IL-1R homologue, now known as the IL-36 Receptor (IL-36R), was identified and these cytokines went through several cycles of renaming with the current nomenclature being proposed in 2010. Despite being identified over 20 years ago, it is only during the last decade that the function of these cytokines in health and disease has really begun to be appreciated, with both homeostatic functions in wound healing and response to infection, as well as pathological functions now ascribed. In the disease context, over activation of IL-36 has now been associated with many inflammatory diseases including Psoriasis and inflammatory bowel diseases, with roles in cancer also now being investigated. This review summarises the current knowledge of IL-36 biology, its role in inflammatory diseases and focuses on an emerging role for IL-36 in cancer.

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“…This therapeutic approach has promoted the research of specific cytokine markers characteristic of the different autoinflammatory pathologies [ 127 , 128 ]: these studies have also enabled the definition of the cross-talk between the different cytokines and the kinetics of secretion during the activation of inflammation ( Figure 1 ).…”

Section: Autoinflammatory Disease: Since the Beginning Of ’90s A New Branch Of Medicinementioning

confidence: 99%

Autoinflammatory Diseases and Cytokine Storms—Imbalances of Innate and Adaptative Immunity

Marcuzzi

Melloni

Zauli

et al. 2021

IJMS

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Innate and adaptive immune responses have a well-known link and represent the distinctive origins of several diseases, many of which may be the consequence of the loss of balance between these two responses. Indeed, autoinflammation and autoimmunity represent the two extremes of a continuous spectrum of pathologic conditions with numerous overlaps in different pathologies. A common characteristic of these dysregulations is represented by hyperinflammation, which is an exaggerated response of the immune system, especially involving white blood cells, macrophages, and inflammasome activation with the hyperproduction of cytokines in response to various triggering stimuli. Moreover, hyperinflammation is of great interest, as it is one of the main manifestations of COVID-19 infection, and the cytokine storm and its most important components are the targets of the pharmacological treatments used to combat COVID-19 damage. In this context, the purpose of our review is to provide a focus on the pathogenesis of autoinflammation and, in particular, of hyperinflammation in order to generate insights for the identification of new therapeutic targets and strategies.

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Exploring the Role of IL-36 Cytokines as a New Target in Psoriatic Disease

Cited by 49 publications

References 58 publications

Pustular Psoriasis: From Pathophysiology to Treatment

Pustular Psoriasis: From Pathophysiology to Treatment

IL-36 cytokines in inflammatory and malignant diseases: not the new kid on the block anymore

Autoinflammatory Diseases and Cytokine Storms—Imbalances of Innate and Adaptative Immunity

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