The pruritogenic role of the type 2 immune response in diseases associated with chronic itch

Ingrasci, Giuseppe; Lipman, Zoe M.; Hawash, Ahmed; Girolomoni, Giampiero; Yosipovitch, Gil

doi:10.1111/exd.14401

Cited by 13 publications

(17 citation statements)

References 108 publications

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“…As more evidence points towards type 2 inflammation as a mechanism for CPUO, with a paradoxical decrease in type 1 inflammation, there has been a heightened interest in therapies that target Th2-associated cytokines such as IL-4, 13, and 31. For example, IL-31 has been found to be significantly increased in the serum of CPUO patients6. Therefore, monoclonal antibodies targeting these Th2 cytokines may block them from exerting further downstream effects that lead to CPUO6,62.…”

Section: Novel Therapiesmentioning

confidence: 99%

“…In the elderly, skin thinning leads to skin barrier dysfunction and reduced reconstitution after damage, leading to loss of fluid retention causing the skin to become more susceptible to pruritus5. Immunosenescence, characterized by a loss of T helper type (Th)-1 cell-driven immune activity and a paradoxical increase in Th2 immune activity in the skin, leads to elevated downstream cytokines IL-4, IL-13, and IL-316, which trigger IgE serum levels, peripheral and tissue eosinophilia, decreased dermal Langerhans cells, and CD8 lymphopenia in CPUO patients compared with age-matched controls7,8. This immune dysregulation further disrupts the epithelial skin barrier and causes more inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutics in chronic pruritus of unknown origin

Labib

Does

et al. 2023

Itch

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Chronic pruritus of unknown origin (CPUO) is a common condition that is underrecognized and underdiagnosed. Patients suffer from 6 or more weeks of pruritus with no identified cause, or with multiple potential causes, of which the primary cause cannot be determined. Despite being a common condition and prevalent in nearly 30% of the elderly in certain populations, most patients suffer from CPUO for years from inadequate treatments for itch and are made to undergo extensive diagnostics. There is no FDA-approved treatment for CPUO, and providers are often tasked to treat CPUO patients with limited knowledge and guidance on CPUO and its treatments. However, recent breakthroughs in antipruritic therapeutics have led to an increase in therapies available for CPUO patients. These include a variety of both pharmacological and nonpharmacological interventions, as well as topical and systemic therapies. Newer therapies such as biologics and Janus kinase inhibitors are currently under investigation due to their therapeutic effects in other pruritic diseases and are promising for treating CPUO. Here, we review the various therapeutic options that are currently available or are on the horizon, with a special emphasis on the therapies antipruritic mechanism, available clinical evidence of efficacy and safety, and the appropriate contexts for their application. By doing so, we hope to educate clinicians on the known treatments for pruritus and their applicability to CPUO to guide optimal management of this highly prevalent disease.

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Section: Novel Therapiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Therapeutics in chronic pruritus of unknown origin

Labib

Does

et al. 2023

Itch

Self Cite

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“…IL-31 is a well-recognized pruritogenic inflammatory cytokine [ 31 ], especially in the pathogenesis of AD [ 32 , 33 ]. It is known that Th2 cells are the main source of IL-31, however, mast cells, eosinophils, basophils, and macrophages are an additional source of IL-31 [ 33 ].…”

Section: Pathogenesismentioning

confidence: 99%

Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment

Wong

Yen

2022

IJMS

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Chronic nodular prurigo (CNPG) is a recalcitrant chronic itchy disorder that affects the quality of life. It can be triggered by multiple etiologies, such as atopic dermatitis, diabetes, and chronic renal diseases. The mechanisms of CNPG are complicated and involved the interaction of the cutaneous, immune, and nervous systems. Diverse immune cells, including eosinophils, neutrophils, T cells, macrophages, and mast cells infiltrated the lesional skin of CNPG, which initiated the inflammatory cytokines and pruritogens release. In addition, the interaction between the immune cells and activated peripheral sensory nerve fibers by neurotransmitters caused neuroinflammation in the skin and intractable itch. This itch-scratch vicious cycle of CNPG results in disease exacerbation. CNPG is difficult to treat with traditional therapies. Recently, great advances have been made in the pathophysiology of both inflammation and pruritus transmission in CNPG. In this review, we summarize the updated mechanisms and novel therapies for CNPG.

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“…IL‐31 is a pruritogenic cytokine produced mainly by Th2 lymphocytes under type 2 inflammation 5 . Some allergic and pruritic skin disorders (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…In this pilot study, we investigated IL‐31 and IL‐31RA expression in each subtype of pemphigus through immunofluorescence staining analysis. We also examined type 2 inflammation‐related pruritogenic proteins: thymic stromal lymphopoietin (TSLP) and periostin, 5 and inflammatory cells, including eosinophils, basophils, and mast cells, as possible participants in the itch sensation 8,9 …”

Section: Introductionmentioning

confidence: 99%

IL‐31 and IL‐31 receptor alpha in pemphigus: Contributors to more than just itch?

Okuno

Hashimoto

Yamazaki

et al. 2023

The Journal of Dermatology

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Pemphigus is an autoimmune blistering disorder with four major subtypes: pemphigus vulgaris (PV), pemphigus vegetans (PVe), pemphigus foliaceus (PF), and pemphigus herpetiformis (PH). Among them, PF and PH present itching as a clinical feature; however, the mechanisms behind the pruritus are still unclear. In this report, we sought to investigate the expression of a type 2 inflammation‐related pruritogenic cytokine IL‐31 and its receptor subunit IL‐31RA through immunofluorescence staining analysis. The number of eosinophils, basophils, and mast cells, and the expression levels of thymic stromal lymphopoietin (TSLP) and periostin were also investigated. Evaluation showed an increase in the number of dermal IL‐31+ cells and IL‐31RA+ cells in PH and PVe. Epidermal expression of IL‐31RA increased in PV, PF, and PVe, but not in PH, compared to healthy individuals. The number of dermal eosinophils and basophils was also increased in PVe and PH. The number of dermal mast cells and expression levels of TSLP and periostin did not change among pemphigus subtypes and healthy controls. Collectively, enhanced IL‐31/IL‐31RA signaling and the increased numbers of dermal eosinophils and basophils may participate in itching in PH. On the other hand, IL‐31/IL‐31RA signaling seemed unable to provoke itching in PVe, a non‐pruritic subtype of pemphigus, although it might contribute to epidermal thickening and dermal fibrosis.

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The pruritogenic role of the type 2 immune response in diseases associated with chronic itch

Cited by 13 publications

References 108 publications

Therapeutics in chronic pruritus of unknown origin

Therapeutics in chronic pruritus of unknown origin

Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment

IL‐31 and IL‐31 receptor alpha in pemphigus: Contributors to more than just itch?

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