Dataset Information

Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch.

ABSTRACT: 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 α_Vβ3 expressed on a subset of sensory neurons as the periostin receptor. Using pharmacological and genetic approaches, we inhibited the function of neuronal integrin α_Vβ3, 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.

SUBMITTER: Mishra SK

PROVIDER: S-EPMC9210348 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch.

Mishra Santosh K SK Wheeler Joshua J JJ Pitake Saumitra S Ding Huiping H Jiang Changyu C Fukuyama Tomoki T Paps Judy S JS Ralph Patrick P Coyne Jacob J Parkington Michelle M DeBrecht Jennifer J Ehrhardt-Humbert Lauren C LC Cruse Glenn P GP Bäumer Wolfgang W Ji Ru-Rong RR Ko Mei-Chuan MC Olivry Thierry T

Cell reports 20200401 1

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 α<sub>V</sub>β3 expressed on a subset of sensory neurons as the periostin receptor. Using pharmacological and genetic approaches, we inhibited the function of neuronal integrin α<sub>V</sub>β3, which ...[more]

PMID: 32268102

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Project description:BackgroundItch sensitization has been reported in patients with chronic allergic skin diseases and observed in a mouse model of allergic contact dermatitis (ACD). There is evidence suggesting that neuroimmune interactions may contribute to itch sensitization, as an increase in dendritic cells (DCs) within ganglia has been observed during allergic conditions. However, how DCs interact with sensory neurons in ganglia during allergic conditions is still not known. This study aims to investigate the role of DCs in dorsal root ganglion (DRG) under ACD conditions, specifically focusing on itch sensitization within the DRG. The tolylene-2,4-diisocyanate (TDI) mouse model for ACD and the co-culture model of DCs and DRG neurons was employed in this study.ResultsWe successfully induced ACD by TDI, as evidenced by the development of edema, elevated total serum IgE levels, and an observed itch reaction in TDI-sensitized mice. Calcium imaging and RT-qPCR analysis revealed that TDI-sensitized mice exhibited signs of peripheral sensitization, including a higher percentage of neurons responding to pruritogens and increased activation and expression of itch receptors in excised DRG of TDI-sensitized mice. Immunofluorescence and flow cytometric analysis displayed an increase of MHCII+ cells, which serves as a marker for DCs, within DRG during ACD. The co-culture study revealed that when DRG neurons were cultured with DCs, there was an increase in the number of neurons responsive to pruritogens and activation of itch receptors such as TRPA1, TRPV1, H1R, and TRPV4. In addition, the immunofluorescence and RT-qPCR study confirmed an upregulation of TRPV4.ConclusionsOur findings indicate that there is an increase of MHCII+ cells and itch peripheral sensitization in DRG under TDI-induced ACD condition. It has been found that MHCII+ cells in DRG might contribute to the itch peripheral sensitization by activating itch receptors, as shown through co-culture studies between DRG neurons and DCs. Further studies are required to identify the specific mediator(s) responsible for peripheral sensitization induced by activated DCs.

Dataset Information

Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch.

Publications

Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch.

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