|  Help  |  About  |  Contact Us

Publication : Leptin receptor signaling sustains metabolic fitness of alveolar macrophages to attenuate pulmonary inflammation.

First Author  Guo Z Year  2022
Journal  Sci Adv Volume  8
Issue  28 Pages  eabo3064
PubMed ID  35857512 Mgi Jnum  J:328324
Mgi Id  MGI:7326692 Doi  10.1126/sciadv.abo3064
Citation  Guo Z, et al. (2022) Leptin receptor signaling sustains metabolic fitness of alveolar macrophages to attenuate pulmonary inflammation. Sci Adv 8(28):eabo3064
abstractText  Alveolar macrophages (AMs) are critical mediators of pulmonary inflammation. Given the unique lung tissue environment, whether there exist AM-specific mechanisms that control inflammation is not known. Here, we found that among various tissue-resident macrophage populations, AMs specifically expressed Lepr, encoding receptor for a key metabolic hormone leptin. AM-intrinsic Lepr signaling attenuated pulmonary inflammation in vivo, manifested as subdued acute lung injury yet compromised host defense against Streptococcus pneumoniae infection. Lepr signaling protected AMs from necroptosis and thus constrained neutrophil recruitment and tissue damage secondary to release of proinflammatory cytokine interleukin-1alpha. Mechanistically, Lepr signaling sustained activation of adenosine monophosphate-activated protein kinase in a Ca(2+) influx-dependent manner and rewired cellular metabolism, thus preventing excessive lipid droplet formation and overloaded metabolic stress in a lipid-rich alveolar microenvironment. In conclusion, our results defined AM-expressed Lepr as a metabolic checkpoint of pulmonary inflammation and exemplified a macrophage tissue adaptation strategy for maintenance of immune homeostasis.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

5 Authors

15 Bio Entities

0 Expression