Adaptive immune responses and protein homeostasis in COPD: the immunoproteasome

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.