The role of TRPV1 in the CD4+ T cell-mediated inflammatory response of allergic rhinitis.

Ramachandran Samivel,Hye Ran Son,Dae Woo Kim,Eyal Raz,Eun Hee Kim,Yun-Hee Rhee,Ji-Hun Mo,Phil-Sang Chung,Ji Hye Kim,Young-Jun Chung,Jun-Sang Bae

doi:10.18632/oncotarget.6653

Abstract

Transient receptor potential vanilloid 1 (TRPV1), which has been identified as a molecular target for the activation of sensory neurons by various painful stimuli, was reported to regulate the signaling and activation of CD4+ T cells. However, the role of TRPV1 in CD4+ T cell in allergic rhinitis remains poorly understood. In this study, TRPV1 expression was localized in CD4+ T cells. Both knockout and chemical inhibition of TRPV1 suppressed Th2/Th17 cytokine production in CD4 T cells and Jurkat T cells, respectively, and can suppress T cell receptor signaling pathways including NF-κB, MAP kinase, and NFAT. In TRPV1 knockout allergic rhinitis (AR) mice, eosinophil infiltration, Th2/Th17 cytokines in the nasal mucosa, and total and ova-specific IgE levels in serum decreased, compared with wild-type AR mice. The TRPV1 antagonists, BCTC or theobromine, showed similar inhibitory immunologic effects on AR mice models. In addition, the number of TRPV1+/CD4+ inflammatory cells increased in the nasal mucosa of patients with AR, compared with that of control subjects. Thus, TRPV1 activation on CD4+ T cells is involved in T cell receptor signaling, and it could be a novel therapeutic target in AR.

Highlights

Transient receptor potential vanilloid 1 (TRPV1) is a polymodal ionic transducer stimulated by a broad range of thermal, mechanical, and chemical stimuli [1]
In double-blinded randomized cross-over studies, the topical intranasal TRPV1 antagonist, SB-705498 did not alleviate allergen-induced or cold dry air-elicited symptoms in allergic or non-allergic rhinitis [9,10,11,12,13]. This mismatch between the over-expression of TRPV1 in nasal mucosa and the lack of clinical efficacy of TRPV1 antagonist treatment draws our attention to a possible alternative target cell type, immune cells
Since CD4+ T cells play a central role in the adaptive immune response, we first assessed whether CD4+ T cells from mice expressed TRPV1

Summary

Introduction

Transient receptor potential vanilloid 1 (TRPV1) is a polymodal ionic transducer stimulated by a broad range of thermal, mechanical, and chemical stimuli [1]. Expression of TRPV1 is markedly up-regulated in the bronchial epithelia and nasal mucosa of patients with refractory asthma [5,6,7]. In double-blinded randomized cross-over studies, the topical intranasal TRPV1 antagonist, SB-705498 did not alleviate allergen-induced or cold dry air-elicited symptoms in allergic or non-allergic rhinitis [9,10,11,12,13]. This mismatch between the over-expression of TRPV1 in nasal mucosa and the lack of clinical efficacy of TRPV1 antagonist treatment draws our attention to a possible alternative target cell type, immune cells. In a recent study, TRPV1 was found to be functionally expressed in CD4+

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