| RRC ID |
76400
|
| Author |
Nakamura Y, Matsumoto H, Wu CH, Fukaya D, Uni R, Hirakawa Y, Katagiri M, Yamada S, Ko T, Nomura S, Wada Y, Komuro I, Nangaku M, Inagi R, Inoue T.
|
| Title |
Alpha 7 nicotinic acetylcholine receptors signaling boosts cell-cell interactions in macrophages effecting anti-inflammatory and organ protection.
|
| Journal |
Commun Biol
|
| 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.
|
| Volume |
6(1)
|
| Pages |
666
|
| Published |
2023-6-23
|
| DOI |
10.1038/s42003-023-05051-2
|
| PII |
10.1038/s42003-023-05051-2
|
| PMID |
37353597
|
| PMC |
PMC10290099
|
| MeSH |
Animals
Anti-Inflammatory Agents / metabolism
Cell Communication
Macrophages / metabolism
Mice
Receptors, Nicotinic* / genetics
Receptors, Nicotinic* / metabolism
alpha7 Nicotinic Acetylcholine Receptor / agonists
alpha7 Nicotinic Acetylcholine Receptor / genetics
alpha7 Nicotinic Acetylcholine Receptor / metabolism
|
| IF |
4.165
|
| Resource |
| Human and Animal Cells |
RAW 264(RCB0535) |
