Sensing Environmental Factors: The Emerging Role of Receptors in Epidermal Homeostasis and Whole-Body Health

Denda, Mitsuhiro

doi:10.1007/978-3-319-43157-4_19

Cited by 3 publications

(4 citation statements)

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“…Much evidence over the past 15 years has now firmly established sensory signaling between epidermal keratinocytes and small caliber axons of primary afferents. 4 , 13 , 41 Here, we present the observation of GluA4 AMPAR in mouse and human keratinocytes. Reverse transcription PCR confirmed Gria4 mRNA expression in FACS-isolated mouse keratinocytes.…”

Section: Discussionmentioning

confidence: 91%

Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities

Cabañero

Irie

Celorrio³

et al. 2016

PR9

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Introduction Epidermal keratinocytes are increasingly recognized as active participants in the sensory transduction of itch and pain, processes known to involve primary afferent glutamatergic neurons. However the role of keratinocyte glutamate signaling in sensory functioning is not fully understood. Here, we present the observation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid type glutamate receptors (AMPAR) in epidermal keratinocytes. Methods Immunohistochemical and in situ hybridization analyses were conducted to assess the expression of AMPAR subunits in epidermal keratinocytes in mouse and human skin samples, and in organotypic cultures of human keratinocytes. In addition, RTPCR further confirmed the expression of GluA4-containing AMPAR in epidermal keratinocytes. Results We found prominent immunolabeling (IL) for the GluA4 subunit of AMPAR in keratinocytes of glabrous and hairy skin of mouse epidermis, as well as in human epidermal keratinocytes. RTPCR confirmed Gria4 transcript expression in epidermal mouse keratinocytes. In addition, expression of GRIA4 mRNA was confirmed in epidermal human keratinocytes by in situ hybridization. Immunohistochemical studies conducted in human skin biopsies from patients with atopic dermatitis (AD) and postherpetic neuralgia (PHN) demonstrate that keratinocyte expression of GluA4 can be altered under pathological conditions. Moreover, a decrease of GluA4 expression was observed in organotypic cultures of human keratinocytes after direct application of algogenic agents. Conclusions We provide evidence that GluA4-containing AMPAR are expressed in epidermal keratinocytes, that human pruritic and painful dermatopathologies have alterations in the keratinocyte expression levels of GluA4-containing AMPAR, and that itch and pain producing substances can directly regulate their production in keratinocytes.

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Section: Discussionmentioning

confidence: 91%

Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities

Cabañero

Irie

Celorrio³

et al. 2016

PR9

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“…The skin ecosystem and its many commensal communities comprise a functional sensory unit which produces previously unrecognized systemic signals through both keratinocytes, specialised antigen presenting cells and the cutaneous immune networks. The recent discovery that the skin is an independent steroidogenic organ, with the capacity to influence whole-body states and emotions [ 46 , 47 ], provides new perspective to the central importance of microbial communities and cutaneous homeostasis. Abnormal skin colonisation may contribute to abnormalities of epithelial development, integrity and predispose to local and systemic immune dysregulation – often first manifest as food allergy and eczema.…”

Section: Discussionmentioning

confidence: 99%

“…However, paradigm-shifting studies have allowed for an entirely different perspective, in which pathology is not entirely mediated in a unidirectional manner from brain to skin. New research places epidermal keratinocytes at the forefront of sensory systems, recognizing that they generate a variety of hormones and neurotransmitters that influence whole-body states and even emotions [ 46 ]. This includes not only the sensors of mechanical stress, temperature and chemical stimuli, but the capacity for glucocorticoid production via elements of the local hypothalamic-pituitary-adrenal (HPA) axis – acting as an independent steroidogenic organ [ 47 ].…”

Section: Introductionmentioning

confidence: 99%

The skin microbiome: impact of modern environments on skin ecology, barrier integrity, and systemic immune programming

Prescott

Larcombe

Logan³

et al. 2017

World Allergy Organization Journal

202

167

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Skin barrier structure and function is essential to human health. Hitherto unrecognized functions of epidermal keratinocytes show that the skin plays an important role in adapting whole-body physiology to changing environments, including the capacity to produce a wide variety of hormones, neurotransmitters and cytokine that can potentially influence whole-body states, and quite possibly, even emotions. Skin microbiota play an integral role in the maturation and homeostatic regulation of keratinocytes and host immune networks with systemic implications. As our primary interface with the external environment, the biodiversity of skin habitats is heavily influenced by the biodiversity of the ecosystems in which we reside. Thus, factors which alter the establishment and health of the skin microbiome have the potential to predispose to not only cutaneous disease, but also other inflammatory non-communicable diseases (NCDs). Indeed, disturbances of the stratum corneum have been noted in allergic diseases (eczema and food allergy), psoriasis, rosacea, acne vulgaris and with the skin aging process. The built environment, global biodiversity losses and declining nature relatedness are contributing to erosion of diversity at a micro-ecological level, including our own microbial habitats. This emphasises the importance of ecological perspectives in overcoming the factors that drive dysbiosis and the risk of inflammatory diseases across the life course.

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“…For example, we and others have shown that keratinocytes express a series of functional thermal receptors, transient receptor potential channels (TRPs) (Inoue et al, 2002, Tsutsumi et al, 2010aTsutsumi et al, 2011b;Denda, 2016). TRPV1 is activated by temperature (>43˚C), capsaicin, and acidic conditions, and activation of TRPV1 induces a sensation of pain (Caterina et al, 1997).…”

Section: Epidermal Keratinocytes As a Complex Sensory Systemmentioning

confidence: 99%

Epidermal Keratinocyte Sensing and Processing of Environmental Information Together with the Brain’s Simulation and Prediction Abilities Helped to Enable <i>Homo sapiens’</i> Evolutionary Success

Denda¹,

Nakanishi²

2020

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Among terrestrial mammals, Homo sapiens has evolved a very specific anatomical feature-very little body hair-thus, the skin surface is exposed directly to the environment. We and others have demonstrated that skin epithelial cells, called keratinocytes, express not only functional sensory systems for a variety of environmental responses, but also a series of neurotransmitter receptors that play key roles in information processing in the brain. Furthermore, the brain cortex is particularly large in Homo sapiens, which has a higher ratio of brain to whole-body weight than any other mammalian species. Here we propose that the evolutionary success and global spread of Homo sapiens are due at least in part to the existence and interaction of these two systems; i.e. the epidermis and brain cortex. First, we discuss the role of the epidermis as a sophisticated organ with multiple sensory inputs and information-processing capabilities, and then we consider the putative requirement for a large brain to carry out simulations and predictions based on input from multiple epidermal systems. We also present some other examples where a functionally sophisticated epidermis is associated with a large brain size. Finally, we discuss possible reasons why Homo sapiens has emerged as the sole surviving human subspecies.

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Sensing Environmental Factors: The Emerging Role of Receptors in Epidermal Homeostasis and Whole-Body Health

Cited by 3 publications

References 68 publications

Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities

Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities

The skin microbiome: impact of modern environments on skin ecology, barrier integrity, and systemic immune programming

Epidermal Keratinocyte Sensing and Processing of Environmental Information Together with the Brain’s Simulation and Prediction Abilities Helped to Enable <i>Homo sapiens’</i> Evolutionary Success

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Sensing Environmental Factors: The Emerging Role of Receptors in Epidermal Homeostasis and Whole-Body Health

Cited by 3 publications

References 68 publications

Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities

Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities

The skin microbiome: impact of modern environments on skin ecology, barrier integrity, and systemic immune programming

Epidermal Keratinocyte Sensing and Processing of Environmental Information Together with the Brain’s Simulation and Prediction Abilities Helped to Enable &lt;i&gt;Homo sapiens’&lt;/i&gt; Evolutionary Success

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Epidermal Keratinocyte Sensing and Processing of Environmental Information Together with the Brain’s Simulation and Prediction Abilities Helped to Enable <i>Homo sapiens’</i> Evolutionary Success