Alpha 7 nicotinic acetylcholine receptors signaling boosts cell-cell interactions in macrophages effecting anti-inflammatory and organ protection

Autor: Yasuna Nakamura, Hirotaka Matsumoto, Chia-Hsien Wu, Daichi Fukaya, Rie Uni, Yosuke Hirakawa, Mikako Katagiri, Shintaro Yamada, Toshiyuki Ko, Seitaro Nomura, Youichiro Wada, Issei Komuro, Masaomi Nangaku, Reiko Inagi, Tsuyoshi Inoue
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Communications Biology, Vol 6, Iss 1, Pp 1-15 (2023)
Druh dokumentu: article
ISSN: 2399-3642
DOI: 10.1038/s42003-023-05051-2
Popis: Abstract Activation of the cholinergic anti-inflammatory pathway (CAP) via vagus nerve stimulation has been shown to improve acute kidney injury in rodent models. While alpha 7 nicotinic acetylcholine receptor (α7nAChR) positive macrophages are thought to play a crucial role in this pathway, their in vivo significance has not been fully understood. In this study, we used macrophage-specific α7nAChR-deficient mice to confirm the direct activation of α7nAChRs in macrophages. Our findings indicate that the administration of GTS-21, an α7nAChR-specific agonist, protects injured kidneys in wild-type mice but not in macrophage-specific α7nAChR-deficient mice. To investigate the signal changes or cell reconstructions induced by α7nAChR activation in splenocytes, we conducted single-cell RNA-sequencing of the spleen. Ligand-receptor analysis revealed an increase in macrophage-macrophage interactions. Using macrophage-derived cell lines, we demonstrated that GTS-21 increases cell contact, and that the contact between macrophages receiving α7nAChR signals leads to a reduction in TNF-α. Our results suggest that α7nAChR signaling increases macrophage-macrophage interactions in the spleen and has a protective effect on the kidneys.
Databáze: Directory of Open Access Journals
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