| RRC ID |
85636
|
| 著者 |
McCright SJ, Harding O, Chini J, DeMarco N, Hung LY, Pastore CF, Lu W, Rabinowitz J, Henao-Mejia J, Herbert DR, Young LR, Hill DA.
|
| タイトル |
Dietary saturated fatty acids promote lung myeloid cell inflammasome activation and IL-1β-mediated inflammation in mice and humans.
|
| ジャーナル |
Sci Transl Med
|
| Abstract |
Resident tissue macrophages and monocytes (RTMs) integrate local and systemic signals to coordinate immune cell function at homeostasis and in response to inflammatory stimuli. Obesity-associated metabolic dysfunction drives the development of RTM populations that contribute to disease states in multiple tissues. However, the contribution of specific dietary components to innate immune cell activation and function, as opposed to the direct effects of obesity, is largely unknown. Here, we studied the mechanisms by which high-fat (HF) diets shape lung RTM phenotype and function at steady state and influence responses to inflammatory insults. We found that, during HF diet feeding, lung RTMs accumulate saturated long-chain fatty acids, specifically stearic acid (SA), and demonstrate features of NLRP3 inflammasome priming and activation. In vivo, increased dietary SA was sufficient to cause neutrophil-predominant lung inflammation in the steady state and exacerbate a model of innate airway inflammation, whereas increased dietary oleic acid, the monounsaturated counterpart of SA, was sufficient to reduce inflammasome activation in the steady state and attenuate airway inflammation. Depletion of interleukin-1β (IL-1β) or pharmacologic inhibition of the endonuclease inositol requiring enzyme 1α (IRE1α) protected against SA-induced exacerbated lung inflammation. Last, we identified a population of lung monocytes with hallmarks of HF diet-induced RTM activation that were present in samples from obese humans with asthma. Together, these results identify a class of dietary lipids that regulate lung RTM phenotype and function in the steady state and modulate the severity of inflammation in the lung.
|
| 巻・号 |
17(813)
|
| ページ |
eadp5653
|
| 公開日 |
2025-8-27
|
| DOI |
10.1126/scitranslmed.adp5653
|
| PMID |
40864681
|
| MeSH |
Animals
Diet, High-Fat
Dietary Fats* / pharmacology
Fatty Acids* / pharmacology
Humans
Inflammasomes* / metabolism
Inflammation* / metabolism
Inflammation* / pathology
Interleukin-1beta* / metabolism
Lung* / pathology
Male
Mice
Mice, Inbred C57BL
Monocytes / drug effects
Monocytes / metabolism
Myeloid Cells* / drug effects
Myeloid Cells* / metabolism
Myeloid Cells* / pathology
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Pneumonia / pathology
|
| IF |
16.304
|
| リソース情報 |
| 実験動物マウス |
RBRC05515 |
