Neuroimmune interactions in chronic itch of atopic dermatitis

Yosipovitch, Gil; Berger, Timothy G.; Fassett, Marlys S.

doi:10.1111/jdv.15973

Cited by 103 publications

(103 citation statements)

References 94 publications

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“…Activation of NK1R via SP leads to multiple signaling cascades involving mast cell degranulation and release of proinflammatory mediators, such as histamine, nerve growth factor expression and leukotriene B4 in keratinocytes and neurogenic inflammation resulting in induction of inflammation and pruritus ( 145 , 146 , 158 ). Several studies investigated the role of SP and NK1R in the pathogenesis of pruritus in various diseases like AD, psoriasis and CSU ( 7 , 159 – 163 ). Recently, it was reported that SP and its receptor NK1R are overexpressed in pruritic AD and psoriatic lesional skin ( 164 ).…”

Section: Receptors In Neuro-immune Interactionsmentioning

confidence: 99%

“…Chronic pruritus in these patients remains a challenge regarding effective anti-pruritic treatments ( 4 ). The physiology of pruritus is transmitted by a complex interaction network of cutaneous and neuronal cells ( 5 – 7 ). Thus, it is very important to understand this network and dynamic processes to identify novel signaling pathways and pruritus mediators.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of Neuro-Immune Interactions in Pruritus With Special Focus on Receptor Expressions

et al. 2021

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Pruritus is a common, but very challenging symptom with a wide diversity of underlying causes like dermatological, systemic, neurological and psychiatric diseases. In dermatology, pruritus is the most frequent symptom both in its acute and chronic form (over 6 weeks in duration). Treatment of chronic pruritus often remains challenging. Affected patients who suffer from moderate to severe pruritus have a significantly reduced quality of life. The underlying physiology of pruritus is very complex, involving a diverse network of components in the skin including resident cells such as keratinocytes and sensory neurons as well as transiently infiltrating cells such as certain immune cells. Previous research has established that there is a significant crosstalk among the stratum corneum, nerve fibers and various immune cells, such as keratinocytes, T cells, basophils, eosinophils and mast cells. In this regard, interactions between receptors on cutaneous and spinal neurons or on different immune cells play an important role in the processing of signals which are important for the transmission of pruritus. In this review, we discuss the role of various receptors involved in pruritus and inflammation, such as TRPV1 and TRPA1, IL-31RA and OSMR, TSLPR, PAR-2, NK1R, H1R and H4R, MRGPRs as well as TrkA, with a focus on interaction between nerve fibers and different immune cells. Emerging evidence shows that neuro-immune interactions play a pivotal role in mediating pruritus-associated inflammatory skin diseases such as atopic dermatitis, psoriasis or chronic spontaneous urticaria. Targeting these bidirectional neuro-immune interactions and the involved pruritus-specific receptors is likely to contribute to novel insights into the underlying pathogenesis and targeted treatment options of pruritus.

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Section: Receptors In Neuro-immune Interactionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Involvement of Neuro-Immune Interactions in Pruritus With Special Focus on Receptor Expressions

et al. 2021

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“…Itch in AD is a result of the complex interplay among many factors including barrier dysfunction and skin inflammation. Although the exact pathogenesis of atopic itch remains unknown, recent studies have revealed hyperinnervation of the epidermis and an increase in several itch mediators/pruritogens in AD 11,12,42 …”

Section: Intense Itch In Admentioning

confidence: 99%

Basics and recent advances in the pathophysiology of atopic dermatitis

Nakahara

Kido‐Nakahara

Tsuji

et al. 2020

The Journal of Dermatology

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Atopic dermatitis is a common, chronic inflammatory skin disease that is characterized by skin barrier dysfunction, inflammation and intense itch. Although the exact mechanisms behind its pathogenesis remain unclear, it is evident that the complex interplay among barrier dysfunction, inflammation and itch are critical in its development, progression and chronicity. Abnormalities in filaggrin, intercellular lipids and tight junctions induce barrier‐disrupted skin, which produces thymic stromal lymphopoietin, interleukin (IL)‐25 and IL‐33; these in turn promote skin inflammation characterized by type 2 immune deviation. This inflammation then downregulates the expression of filaggrin in keratinocytes and exacerbates epidermal barrier dysfunction. Furthermore, various itch mediators/pruritogens produced during this inflammatory process can act directly on sensory nerves and cause itch. In this review, we summarize the basics and recent advances in our understanding of the pathophysiology of atopic dermatitis focusing on three aspects: barrier dysfunction, skin inflammation and itch.

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“…Two major neuronal pathways are mentioned: histaminergic and non-histaminergic, with the latter mainly associated with CP [6]. CP in the course of AD (serving as an example of a 'classic' itchy disorder) may be regarded as a result of crosstalk between nervous system, cutaneous immune system and keratinocyte populations [7]. The crucial pathogenetic aspects of CP, such as the interactions between various pruritogens and their receptors, and the description of itch pathways with regard to peripheral nervous system (PNS) and central nervous system (CNS) processing in different regions, including neural sensitization, have been reviewed in great detail by Yosipovitch et al [6,7].…”

Section: Introductionmentioning

confidence: 99%

Emerging Therapeutic Options for Chronic Pruritus

2020

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Chronic pruritus, defined as an unpleasant sensation resulting in a need to scratch that lasts more than 6 weeks, is a prevalent and bothersome symptom associated with both cutaneous and systemic conditions. Due to complex pathogenesis and profuse contributing factors, chronic pruritus therapy remains challenging. Regardless of the well-established antipruritic properties of classic pharmacotherapy (topical therapy, phototherapy and systemic therapy), these methods often provide insufficient relief for affected individuals. Owing to the growing interest in the field of pruritic research, further experimental and clinical data have emerged, continuously supporting the possibility of instigating novel therapeutic measures. This review covers the most relevant current modalities remaining under investigation that possess promising perspectives of approval in the near future, especially opioidergic drugs (mu-opioid antagonists and kappa-opioid agonists), neurokinin-1 receptor antagonists, biologic drugs, Janus kinase inhibitors, ileal bile acid transporter inhibitors, aryl hydrocarbon receptor agonists and histamine H 4 receptor antagonists.

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Neuroimmune interactions in chronic itch of atopic dermatitis

Cited by 103 publications

References 94 publications

Involvement of Neuro-Immune Interactions in Pruritus With Special Focus on Receptor Expressions

Involvement of Neuro-Immune Interactions in Pruritus With Special Focus on Receptor Expressions

Basics and recent advances in the pathophysiology of atopic dermatitis

Emerging Therapeutic Options for Chronic Pruritus

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