Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch
Summary: Chronic allergic itch is a common symptom affecting millions of people and animals, but its pathogenesis is not fully explained. Herein, we show that periostin, abundantly expressed in the skin of patients with atopic dermatitis (AD), induces itch in mice, dogs, and monkeys. We identify the...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720303508 |
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doaj-d9a4e1d17b0e47259c72065d38768e71 |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Santosh K. Mishra Joshua J. Wheeler Saumitra Pitake Huiping Ding Changyu Jiang Tomoki Fukuyama Judy S. Paps Patrick Ralph Jacob Coyne Michelle Parkington Jennifer DeBrecht Lauren C. Ehrhardt-Humbert Glenn P. Cruse Wolfgang Bäumer Ru-Rong Ji Mei-Chuan Ko Thierry Olivry |
| spellingShingle |
Santosh K. Mishra Joshua J. Wheeler Saumitra Pitake Huiping Ding Changyu Jiang Tomoki Fukuyama Judy S. Paps Patrick Ralph Jacob Coyne Michelle Parkington Jennifer DeBrecht Lauren C. Ehrhardt-Humbert Glenn P. Cruse Wolfgang Bäumer Ru-Rong Ji Mei-Chuan Ko Thierry Olivry Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch Cell Reports |
| author_facet |
Santosh K. Mishra Joshua J. Wheeler Saumitra Pitake Huiping Ding Changyu Jiang Tomoki Fukuyama Judy S. Paps Patrick Ralph Jacob Coyne Michelle Parkington Jennifer DeBrecht Lauren C. Ehrhardt-Humbert Glenn P. Cruse Wolfgang Bäumer Ru-Rong Ji Mei-Chuan Ko Thierry Olivry |
| author_sort |
Santosh K. Mishra |
| title |
Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch |
| title_short |
Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch |
| title_full |
Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch |
| title_fullStr |
Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch |
| title_full_unstemmed |
Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch |
| title_sort |
periostin activation of integrin receptors on sensory neurons induces allergic itch |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2020-04-01 |
| description |
Summary: Chronic allergic itch is a common symptom affecting millions of people and animals, but its pathogenesis is not fully explained. Herein, we show that periostin, abundantly expressed in the skin of patients with atopic dermatitis (AD), induces itch in mice, dogs, and monkeys. We identify the integrin αVβ3 expressed on a subset of sensory neurons as the periostin receptor. Using pharmacological and genetic approaches, we inhibited the function of neuronal integrin αVβ3, which significantly reduces periostin-induced itch in mice. Furthermore, we show that the cytokine TSLP, the application of AD-causing MC903 (calcipotriol), and house dust mites all induce periostin secretion. Finally, we establish that the JAK/STAT pathway is a key regulator of periostin secretion in keratinocytes. Altogether, our results identify a TSLP-periostin reciprocal activation loop that links the skin to the spinal cord via peripheral sensory neurons, and we characterize the non-canonical functional role of an integrin in itch. : Mishra et al. demonstrate periostin-induced itch in mice, dogs, and monkeys and identify the integrin αVβ3 as the periostin neuronal receptor. They find that keratinocytes release periostin in response to TSLP, thus identifying a possible reciprocal vicious circle implicating the cytokine TSLP and periostin in chronic allergic itch. Keywords: atopic dermatitis, AD, chronic allergic itch, integrin, JAK/STAT, keratinocytes, NPPB, periostin, sensory neuron, TRPV1, TRPA1, TSLP |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124720303508 |
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doaj-d9a4e1d17b0e47259c72065d38768e712020-11-25T03:32:25ZengElsevierCell Reports2211-12472020-04-01311Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic ItchSantosh K. Mishra0Joshua J. Wheeler1Saumitra Pitake2Huiping Ding3Changyu Jiang4Tomoki Fukuyama5Judy S. Paps6Patrick Ralph7Jacob Coyne8Michelle Parkington9Jennifer DeBrecht10Lauren C. Ehrhardt-Humbert11Glenn P. Cruse12Wolfgang Bäumer13Ru-Rong Ji14Mei-Chuan Ko15Thierry Olivry16Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA; The WM Keck Behavioral Center, North Carolina State University, Raleigh, NC, USA; Program in Genetics, North Carolina State University, Raleigh, NC, USA; Corresponding authorDepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USADepartment of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USADuke University, Durham, NC, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USADepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; Institute of Pharmacology and Toxicology, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, GermanyDuke University, Durham, NC, USADepartment of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USAComparative Medicine Institute, North Carolina State University, Raleigh, NC, USA; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASummary: Chronic allergic itch is a common symptom affecting millions of people and animals, but its pathogenesis is not fully explained. Herein, we show that periostin, abundantly expressed in the skin of patients with atopic dermatitis (AD), induces itch in mice, dogs, and monkeys. We identify the integrin αVβ3 expressed on a subset of sensory neurons as the periostin receptor. Using pharmacological and genetic approaches, we inhibited the function of neuronal integrin αVβ3, which significantly reduces periostin-induced itch in mice. Furthermore, we show that the cytokine TSLP, the application of AD-causing MC903 (calcipotriol), and house dust mites all induce periostin secretion. Finally, we establish that the JAK/STAT pathway is a key regulator of periostin secretion in keratinocytes. Altogether, our results identify a TSLP-periostin reciprocal activation loop that links the skin to the spinal cord via peripheral sensory neurons, and we characterize the non-canonical functional role of an integrin in itch. : Mishra et al. demonstrate periostin-induced itch in mice, dogs, and monkeys and identify the integrin αVβ3 as the periostin neuronal receptor. They find that keratinocytes release periostin in response to TSLP, thus identifying a possible reciprocal vicious circle implicating the cytokine TSLP and periostin in chronic allergic itch. Keywords: atopic dermatitis, AD, chronic allergic itch, integrin, JAK/STAT, keratinocytes, NPPB, periostin, sensory neuron, TRPV1, TRPA1, TSLPhttp://www.sciencedirect.com/science/article/pii/S2211124720303508 |