Buddy, bystander or betrayer: B cells in lymphoid aggregates in AATD emphysema

This is the authors' abstract. We don't add key points for this paper.

Extract Alpha-1 antitrypsin (AAT) is a major serine protease inhibitor, protecting lung tissue against the destructive effects of (chronic) release of neutrophil elastase by degranulating neutrophils during inflammation. Over the past decade, other anti-inflammatory properties of AAT have become more apparent, including regulation of human neutrophil chemotaxis [1], suppression of interferon-γ-induced M1 macrophage activation/polarisation [2], and attenuation of nuclear factor-κB activation in lung epithelial cells [3]. Alpha-1 antitrypsin deficiency (AATD) is the most widely recognised genetic disorder causing early-onset emphysema. The Z-mutation of AAT (Z-AAT) comprises more than 85% of the mutations leading to severe AATD due to accumulation of Z-AAT polymers inside hepatocytes, leading to lowered circulating AAT levels. In the past decades, the main research focus in the pathophysiology of AATD has been on protease/anti-protease imbalance and epithelial cell damage; however, it has become clear that AAT has pleiotropic functions, including the above-mentioned anti-inflammatory actions, but also modification of B cell responses [4]. This is relevant, since the mechanism of AATD-induced emphysema is suggested to be more complex, involving the adaptive immune system [5].