| Title: |
Dietary saturated fatty acids promote lung myeloid cell inflammasome activation and IL-1β–mediated inflammation in mice and humans. |
| Authors: |
McCright, Sam J.; Harding, Olivia; Chini, Julia; DeMarco, Nicole; Hung, Li-Yin; Pastore, Christopher F.; Lu, Wenyun; Rabinowitz, Joshua; Henao-Mejia, Jorge; Herbert, De'Broski R.; Young, Lisa R.; Hill, David A. |
| Source: |
Science Translational Medicine; 8/27/2025, Vol. 17 Issue 813, p1-15, 15p |
| Subject Terms: |
Saturated fatty acids; Macrophages; Immune response; Asthma; Myeloid cells; Interleukin-1; Obesity; Lung infections |
| 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. Editor's summary: It is becoming increasingly understood that our diets affect much more than weight. Here, McCright et al. found that a high-fat diet, and specifically a diet rich in long-chain fatty acids, influenced the immunological tone of lung resident tissue macrophages and monocytes (RTMs) in mice. High-fat diet or a stearic acid–enriched diet elicited lung inflammation at steady state in the mice and worsened disease in a model of airway inflammation. A similar inflammatory population of macrophages was observed in bronchoalveolar lavage fluid from humans with obesity-associated asthma, suggesting that this pathway is conserved and that long-chain fatty acids may potentiate this particular type of asthma in humans. —Courtney Malo [ABSTRACT FROM AUTHOR] |
| : |
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| Database: |
Complementary Index |