Connections between Immune-Derived Mediators and Sensory Nerves for Itch Sensation

Toyama, Sumika; Tominaga, Mitsutoshi; Takamori, Kenji

doi:10.3390/ijms222212365

Cited by 12 publications

(10 citation statements)

References 157 publications

(223 reference statements)

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“…A parte de la histamina, existen múltiples otras sustancias que se liberan durante la reacción inflamatoria tipo 2, que pueden estimular las terminaciones nerviosas cutáneas del prurito, de manera directa o indirecta. Se pueden mencionar la IL-4, IL-13 e IL-31, entre otras 24 . También la TSLP, derivada de los queratinocitos y algunas células inflamatorias, puede estimular los pruriceptores fijándose a su receptor TSLPR, un heterodímero señalizando mediante JAK1-2 25 .…”

Section: Mecanismos Del Pruritounclassified

“…Las terminaciones de los axones en la epidermis, que inician en el soma en el ganglio de la raíz dorsal tienen receptores para histamina, pero también para una gran variedad de citocinas y otras sustancias. Así, se han descrito las fibras nerviosas 1 (NP1, de non-peptidergic [NP] nociceptor clusters), que tienen, entre otras, receptores para IL-4 e IL-13; las fibras NP2 con receptores para IL 4, IL 13 e histamina y las fibras NP3 con receptores para estos tres al igual que para IL-31 y leucotrieno C 4 24 . Estas citocinas se liberan desde la células inflamatorias en la piel dañada del paciente con DA, como son los linfocitos ILC2, Th2, los eosinófilos y las células cebadas.…”

Section: Mecanismos Del Pruritounclassified

See 1 more Smart Citation

Guía de dermatitis atópica para México (GUIDAMEX): lineamientos usando metodología ADAPTE

Larenas‐Linnemann¹,

Rincón-Pérez²,

Luna-Pech³

et al. 2023

GMM

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Section: Mecanismos Del Pruritounclassified

Guía de dermatitis atópica para México (GUIDAMEX): lineamientos usando metodología ADAPTE

Larenas‐Linnemann¹,

Rincón-Pérez²,

Luna-Pech³

et al. 2023

GMM

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“…Mast cells are predominantly known for their role in histaminergic itch, but also secrete other pruritogens such as the lipid mediators leukotriene B4 and C4, itch-associated cytokines IL-4, 13, 31, 33 and proteases (tryptase, cathepsin S) that activate PAR2 ( Toyama et al, 2021 ).…”

Section: Cell Types and Receptors Involved In Itchmentioning

confidence: 99%

“…Similar to mast cells, basophils ( Hashimoto et al, 2019 ), eosinophils ( Radonjic-Hoesli et al, 2021 ), neutrophils ( Hashimoto et al, 2018 ), dendritic cells and macrophages all share the ability to release pruritogenic substances and likely contribute to itch ( Toyama et al, 2021 ), especially in immune cell-enriched inflamed skin ( Nguyen and Soulika, 2019 ).…”

Section: Cell Types and Receptors Involved In Itchmentioning

confidence: 99%

In vitro models for investigating itch

Mießner

Seidel²,

Smith³

2022

Front. Mol. Neurosci.

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Itch (pruritus) is a sensation that drives a desire to scratch, a behavior observed in many animals. Although generally short-lasting and not causing harm, there are several pathological conditions where chronic itch is a hallmark symptom and in which prolonged scratching can induce damage. Finding medications to counteract the sensation of chronic itch has proven difficult due to the molecular complexity that involves a multitude of triggers, receptors and signaling pathways between skin, immune and nerve cells. While much has been learned about pruritus from in vivo animal models, they have limitations that corroborate the necessity for a transition to more human disease-like models. Also, reducing animal use should be encouraged in research. However, conducting human in vivo experiments can also be ethically challenging. Thus, there is a clear need for surrogate models to be used in pre-clinical investigation of the mechanisms of itch. Most in vitro models used for itch research focus on the use of known pruritogens. For this, sensory neurons and different types of skin and/or immune cells are stimulated in 2D or 3D co-culture, and factors such as neurotransmitter or cytokine release can be measured. There are however limitations of such simplistic in vitro models. For example, not all naturally occurring cell types are present and there is also no connection to the itch-sensing organ, the central nervous system (CNS). Nevertheless, in vitro models offer a chance to investigate otherwise inaccessible specific cell–cell interactions and molecular pathways. In recent years, stem cell-based approaches and human primary cells have emerged as viable alternatives to standard cell lines or animal tissue. As in vitro models have increased in their complexity, further opportunities for more elaborated means of investigating itch have been developed. In this review, we introduce the latest concepts of itch and discuss the advantages and limitations of current in vitro models, which provide valuable contributions to pruritus research and might help to meet the unmet clinical need for more refined anti-pruritic substances.

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“…The pathophysiology of AD consists of complex interactions between epidermal barrier disruption, skin microbiota dysbiosis, and altered type 2 immune responses [ 8 , 9 ]. Chronic itch is known as one of the main symptoms in AD patients especially via non-histaminergic itch signaling pathways, which usually persists despite the administration of medication [ 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

An Altered Skin and Gut Microbiota Are Involved in the Modulation of Itch in Atopic Dermatitis

Moniaga

Tominaga

Takamori

2022

Cells

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Skin and gut microbiota play an important role in the pathogenesis of atopic dermatitis (AD). An alteration of the microbiota diversity modulates the development and course of AD, e.g., decreased microbiome diversity correlates with disease severity, particularly in lesional skin of AD. Itch is a hallmark of AD with unsatisfying treatment until now. Recent evidence suggests a possible role of microbiota in altering itch in AD through gut–skin–brain interactions. The microbial metabolites, proinflammatory cytokines, and impaired immune response lead to a modulation of histamine-independent itch, disruption of epidermal barrier, and central sensitization of itch mechanisms. The positive impact of probiotics in alleviating itch in AD supports this hypothesis, which may lead to novel strategies for managing itchy skin in AD patients. This review summarizes the emerging findings on the correlation between an altered microbiota and gut–skin–brain axis in AD, especially in modulating itchy skin.

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Connections between Immune-Derived Mediators and Sensory Nerves for Itch Sensation

Cited by 12 publications

References 157 publications

Guía de dermatitis atópica para México (GUIDAMEX): lineamientos usando metodología ADAPTE

Guía de dermatitis atópica para México (GUIDAMEX): lineamientos usando metodología ADAPTE

In vitro models for investigating itch

An Altered Skin and Gut Microbiota Are Involved in the Modulation of Itch in Atopic Dermatitis

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