![]() ![]() ![]() 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. However, the functional significance of tissue microarchitecture, cellular composition, and individual LNs in the "LN chain" system is not fully understood. Moreover, an intermittently arranged LN in the lymphatic pathway is considered to cooperatively prevent lymph-borne substances from entering blood circulation. The filtering function of LNs involves resident macrophages tightly associated with unique lymphatic sinus structures. In the lymphatic vascular system, lymph nodes (LNs) play a pivotal role in filtering and removing lymph-borne substances. Madoka Ozawa, Shihori Nakajima, Daichi Kobayashi, Koichi Tomii, Nan-Jun Li, Tomoya Watarai, Ryo Suzuki, Satoshi Watanabe, Yasuhiro Kanda, Arata Takeuchi, Tomoya Katakaiįrontiers in cell and developmental biology Micro- and Macro-Anatomical Frameworks of Lymph Nodes Indispensable for the Lymphatic System Filtering Function. 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. 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. 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. 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. However, the role of Tas2Rs in immune cells remains controversial. Recent evidence suggests that Tas2Rs are also expressed extraorally, including in immune cells. 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. Tas2R signaling enhances mouse neutrophil migration via a ROCK-dependent pathwayĭaichi Kobayashi, Tomoya Watarai, Madoka Ozawa, Yasuhiro Kanda, Fumihiro Saika, Norikazu Kiguchi, Arata Takeuchi, Masahito Ikawa, Shinsuke Matsuzaki, Tomoya Katakai Therefore, B cells are promising targets, but the spatiotemporal balance of the subsets that exhibit opposite characteristics, that is, the protumor or antitumor state in TDLNs, should be understood, and strategies to separately control their functions should be developed to maximize the clinical outcome. Given that the presence of B cells in tumor tissues may reflect the ongoing antitumor response in TDLNs, therapeutic induction and enhancement of these lymphocytes are expected to increase the overall effectiveness of immunotherapy. In contrast, B cell infiltration and formation of tertiary lymphoid structures in tumors are positively correlated with therapeutic prognosis, suggesting that tumor antigen-specific activation of B cells and antibody production are advantageous for antitumor immunity in mid- to late-stage tumors. Therefore, triggering and enhancing antitumor responses by immunotherapies require selective control of these regulatory B cell subsets in TDLNs. In tumor-draining lymph nodes (TDLNs), tumor antigen-reactive B cells potentially acquire immunoregulatory phenotypes and contribute to an immunosuppressive microenvironment. If tumor cells can evade immune attack at an early stage, non-destructive responses, such as tolerance and immunosuppression, are established over time. Unlike responses against microbial or pathogenic infections, tumor cells are derived from autologous cells that have mutated and become aberrant thus, elimination by the adaptive immune system is essentially inefficient. However, this complicated situation likely depends on the temporal and spatial relationship between the developing tumor and B cells that recognize tumor antigens. ![]() The role of B cells in antitumor immunity has been reported to be either promotive or suppressive, but the specific mechanism remains to be comprehensively understood. Publishing type:Research paper (scientific journal) ![]()
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