Tas2R signaling enhances mouse neutrophil migration via a ROCK-dependent pathway

Abstract

Type-2 bitter taste receptors (Tas2Rs) are a large family of G protein-coupled receptors that are expressed in the oral cavity and serve to detect substances with bitter tastes in foods and medicines. Recent evidence suggests that Tas2Rs are also expressed extraorally, including in immune cells. However, the role of Tas2Rs in immune cells remains controversial. Here, we demonstrate that Tas2R126, Tas2R135, and Tas2R143 are expressed in mouse neutrophils, but not in other immune cells such as macrophages or T and B lymphocytes. Treatment of bone marrow-derived neutrophils from wild-type mice with the Tas2R126/143 agonists arbutin and d-salicin led to enhanced C-X-C motif chemokine ligand 2 (CXCL2)-stimulated migration in vitro, but this response was not observed in neutrophils from Tas2r126/135/143-deficient mice. Enhancement of CXCL2-stimulated migration by Tas2R agonists was accompanied by increased phosphorylation of myosin light chain 2 (MLC2) and was blocked by pretreatment of neutrophils with inhibitors of Rho-associated coiled-coil-containing protein kinase (ROCK), but not by inhibitors of the small GTPase RhoA. Taken together, these results demonstrate that mouse neutrophils express functional Tas2R126/143 and suggest a role for Tas2R126/143–ROCK–MLC2-dependent signaling in the regulation of neutrophil migration.

Bitter taste receptors in the reproductive system: Function and therapeutic implications

“…Only a few Tas2rs , including Tas2r131 and the Tas2r143/Tas2r135/Tas2r126 cluster, have been tagged genetically in mice (Liu et al, 2017; Voigt et al, 2015). Similarly, only a handful of Tas2r knockout mice involving Tas2r105 and the Tas2r143/Tas2r135/Tas2r126 cluster have been generated in different laboratories (Kobayashi et al, 2022; Lu et al, 2021; Mueller et al, 2005; Perniss et al, 2020). Notably, no cell‐specific knockout mouse has been reported yet.…”

“…While qRT-PCR is a reliable and sensitive technique utilized to (Kolodziejczyk et al, 2015) and spatial transcriptomics (Marx, 2021).…”

“…Clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR‐associated endonuclease 9 (Cas9) gene editing technology, known for its efficacy in targeting multiple genes simultaneously (Wang et al, 2013; Xie et al, 2015) was used by our team and two other groups to generate Tas2r143/Tas2r135/Tas2r126 cluster deletion mice (Kobayashi et al, 2022; Lu et al, 2021; Perniss et al, 2020). With 35 Tas2rs located in multiple clusters on the mouse chromosome, it is feasible to create a Tas2r ‐less mouse through a series of stepwise applications of CRISPR/Cas9.…”

Interkingdom Detection of Bacterial Quorum-Sensing Molecules by Mammalian Taste Receptors

“…Gram-negative AHLs have been shown to be able to activate other T2Rs than T2R38, including isoforms T2R10 and T2R14 when expressed in HEK93 cells [ 202 ]. In addition to their expression in sinonasal epithelial cells, T2Rs were also identified in immune cells where they may contribute to the detection of quorum sensing molecules [ 203 , 204 , 205 , 206 , 207 , 208 ]. We demonstrated that unprimed macrophages (M0) can be activated by AHLs or quinolones through T2R receptors.…”

The Complex Journey of the Calcium Regulation Downstream of TAS2R Activation

“…However, in macrophages [ 28 ], the transcripts of at least 16 different subtypes (TAS2Rs 3, 4, 5, 7, 8, 9, 10, 14, 19, 20, 31, 38, 39, 43, 45 and 46) have been detected. Both in resident and monocyte-derived macrophages, bitter agonists inhibit cytokine release [ 58 ] and cell migration [ 85 , 86 ] and stimulate reactive species release [ 61 ]. In mast cells, TAS2R3, 4, 10, 14 and 46 are well-expressed and are hypothesized to exert an inhibitory function on leukocytes, particularly by counteracting the release of histamine in IgE-activated cells [ 87 , 88 ].…”