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Francesca Polverino

European Respiratory Journal 2022 59: 2102557; DOI: 10.1183/13993003.02557-2021

Extract

Whether exaggerated immune responses cause inflammation-derived damage in COPD or whether the cigarette smoke-induced inflammatory cascade is the ultimate cause of the immune system activation in COPD is a never-ending chicken-and-egg debate. In any case, the era when COPD pathogenesis seemed to revolve solely around CD8+ T cells and macrophages seems long gone. As the resources to dissect cellular biology advance, we have shifted our magnifying glass from the main cell types characterising a specific disease, to their subcellular functions. In particular, recent studies pointed at mechanisms involving altered protein homeostasis (proteostasis), such as unfolded protein responses and endoplasmic reticulum stress, and inhibition of the ubiquitin-proteasome system, as key in COPD pathogenesis [1, 2]. This dysfunctional protein processing ultimately leads to the accumulation of nonfunctional and potentially cytotoxic, misfolded proteins that contribute to lung cell apoptosis, inflammation and autophagy typical of COPD.

The immunoproteasome function and activity are increased in circulating immune cells in end-stage COPD. The immunoproteasome represents a link between adaptive immune activation and protein homeostasis typical of the COPD lung. https://bit.ly/3B99U8N

Footnotes

• Conflict of interest: F. Polverino reports support for travel to McMaster University (Hamilton, ON, Canada), Baylor College of Medicine (Houston, TX, USA) and Cincinnati Children's Hospital (Cincinnati, OH, USA).

• Support statement: F. Polverino is supported by the Asthma and Airway Disease Research Center Funds, and the NIH/NHLBI (HL149744 and HL132523) research grants. Funding information for this article has been deposited with the Crossref Funder Registry.

• Received September 23, 2021.
• Accepted September 24, 2021.

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