Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling

• Published in: eLife Vol. 7
• Main Authors: Moehring, Francie, Cowie, Ashley M, Menzel, Anthony D, Weyer, Andy D, Grzybowski, Michael, Arzua, Thiago, Geurts, Aron M, Palygin, Oleg, Stucky, Cheryl L
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 16-01-2018; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Adenosine Triphosphate - metabolism; Animals; cell sniff; Cells, Cultured; Clonal deletion; Drug development; Eczema; Epidermis; Gene expression; Genotype & phenotype; Growth factors; Humans; Information management; Keratinocytes; Keratinocytes - physiology; Light; mechanotransduction; Mice, Inbred C57BL; Mice, Knockout; Neurons; Neuroscience; Neurosciences; Novels; Optogenetics; Pain; Pain management; Psoriasis; purinoceptors; Receptors, Purinergic P2X4 - metabolism; Sensory neurons; Signal Transduction; Skin; Skin care products; Skin diseases; tactile; Tactile stimuli; Therapeutics; Touch; Canada; United States > US; mouse; mechanotransduction; neuroscience; tactile; optogenetics; cell sniff; purinoceptors; epidermis
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.31684

The first point of our body's contact with tactile stimuli (innocuous and noxious) is the epidermis, the outermost layer of skin that is largely composed of keratinocytes. Here, we sought to define the role that keratinocytes play in touch sensation in vivo and ex vivo. We show that optogenetic inhibition of keratinocytes decreases behavioral and cellular mechanosensitivity. These processes are inherently mediated by ATP signaling, as demonstrated by complementary cutaneous ATP release and degradation experiments. Specific deletion of P2X4 receptors in sensory neurons markedly decreases behavioral and primary afferent mechanical sensitivity, thus positioning keratinocyte-released ATP to sensory neuron P2X4 signaling as a critical component of baseline mammalian tactile sensation. These experiments lay a vital foundation for subsequent studies into the dysfunctional signaling that occurs in cutaneous pain and itch disorders, and ultimately, the development of novel topical therapeutics for these conditions.