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.

In the lymphatic vascular system, lymph nodes (LNs) play a pivotal role in filtering and removing lymph-borne substances. The filtering function of LNs involves resident macrophages tightly associated with unique lymphatic sinus structures. Moreover, an intermittently arranged LN in the lymphatic pathway is considered to cooperatively prevent lymph-borne substances from entering blood circulation. However, the functional significance of tissue microarchitecture, cellular composition, and individual LNs in the “LN chain” system is not fully understood. To explore the mechanistic and histo-anatomical significance of LNs as lymph fluid filters, we subcutaneously injected fluorescent tracers into mice and examined the details of lymphatic transport to the LNs qualitatively and quantitatively. Lymph-borne tracers were selectively accumulated in the MARCO+ subcapsular-medullary sinus border (SMB) region of the LN, in which reticular lymphatic endothelial cells and CD169+F4/80+ medullary sinus macrophages construct a dense meshwork of the physical barrier, forming the main body to capture the tracers. We also demonstrated stepwise filtration via the LN chain in the lymphatic basin, which prevented tracer leakage into the blood. Furthermore, inflammatory responses that induce the remodeling of LN tissue as well as the lymphatic pathway reinforce the overall filtering capacity of the lymphatic basin. Taken together, specialized tissue infrastructure in the LNs and their systematic orchestration constitute an integrated filtering system for lymphatic recirculation.