Bitter taste is mediated by bitter taste receptors (T2Rs), a multigene family of G-protein-coupled receptors on the tongue. 25 different T2Rs are known to be expressed. T2Rs have recently been found in several regions of the body, and T2R38 has been reported to be expressed on lymphocytes in peripheral blood. Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, and skin-infiltrating T cells play a pivotal role in the development and maintenance of AD. C-C chemokine receptor type4 (CCR4) and type10 (CCR10) are selectively expressed on skin lymphocytes and are important GPCRs that positively regulate the lymphocytes homing to the skin. However, literatures using deficient mice suggest that homing to the skin cannot be explained by CCR4 and CCR10 alone, suggesting other molecules that regulate homing. Given that most of the molecules involved in lymphocyte infiltration are GPCRs, it is possible that T2R38 regulates the trafficking of different leukocyte subsets into skin. We first confirmed that the expression of the T2R38 was higher in lesional skin of AD patients than in healthy controls. Furthermore, skin T2R38 expression levels in AD patients correlated with serum thymus and activation-regulated chemokine and IgE levels. Section staining in lesional skin revealed that CD3+ T cells in the dermis were T2R38 positive. Flow cytometric analysis consistently confirmed the expression of T2R38 in skin T cells. Migration assay using T2R38-transduced Jurkat T-cell leukemia cells revealed that T2R38 agonists exerted migration inhibitory effects in a dose-dependent manner. Notably, skin tissue extracts and supernatants from cultured HaCaT keratinocytes caused T2R38-dependent migration inhibition, indicating an endogenous ligand for T2R38 in the skin epidermis. These findings implicate that T2R38 negatively regulates the migration of skin-infiltrating lymphocytes and can be a therapeutic target for inflammatory skin diseases.

ESDR338 - Bitter taste receptor T2R38 expressed on skin-infiltrating lymphocytes regulates lymphocyte migration

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.