The Expression and Function of the Ectopic Olfactory Receptor OR10G7 in Atopic Dermatitis

Publication date: Available online 14 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Elizabeth Huiwen Tham, Nathan Dyjack, Byung Eui Kim, Cydney Rios, Max A. Seibold, Donald YM. Leung, Elena Goleva

Abstract

Background

Ectopic olfactory receptors (OR) are found in the skin but their expression and biological functions in normal skin and atopic dermatitis (AD) are unknown.

Objectives

To characterize the expression of ORs in the skin and assess OR-mediated biological responses of primary human keratinocytes in the presence of odorant ligands.

Methods

OR expression was examined by whole transcriptome sequencing of skin tape strips collected from AD and healthy controls (NC). OR10G7 and FLG-1 expression were analyzed by RT-PCR and immunostaining in AD and NC skin biopsies and primary human keratinocytes. ATP and cyclic AMP production by control and OR10G7 siRNA transfected keratinocytes in response to odorant stimulation with acetophenone and eugenol were assessed.

Results

A total of 381 OR gene transcripts were detected in the skin samples, with the greatest OR expression detected in the skin tape strips, corresponding to the upper granular layer of the skin. OR10G7 expression was significantly increased in AD compared to NC skin biopsies (p=0.01) and inversely correlated with FLG-1 expression (p=0.009). OR10G7 expression was highest in undifferentiated AD keratinocytes and was down-regulated with progressive differentiation. Primary human keratinocytes produced ATP, an essential neurotransmitter in sensory pathways, in response to acetophenone and eugenol, odorants previously identified as potential ligands for this receptor. This response was abolished in OR10G7 siRNA-transfected keratinocytes.

Conclusions

OR10G7 is expressed at significantly higher levels in undifferentiated AD keratinocytes compared to normal controls. OR10G7 is likely involved in the transmission of skin-induced chemosensory responses to odorant stimulation, which may modulate differential nociceptive responses in AD skin.

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