What's the deal with efferocytosis and asthma?

Mucosal sites, such as the lung, serve as crucial, yet vulnerable barriers to environmental insults such as pathogens, allergens, and toxins. Often, these exposures induce massive infiltration and death of short-lived immune cells in the lung, and efficient clearance of these cells is important for preventing hyperinflammation and resolving immunopathology. Herein, we review recent advances in our understanding of efferocytosis, a process whereby phagocytes clear dead cells in a noninflammatory manner. We further discuss how efferocytosis impacts the onset and severity of asthma in humans and mammalian animal models of disease. Finally, we explore how recently identified genetic perturbations or biological pathway modulations affect pathogenesis and shed light on novel therapies aimed at treating or preventing asthma. Efferocytosis is a carefully orchestrated process that requires dying cells to release and display signals to facilitate recruitment of and recognition by phagocytes. Efferocytosis is characterized by its immunotolerant response, and defects in the efferocytotic machinery are associated with autoimmune and inflammatory disorders in mice and humans. Asthma affects over 200 million people worldwide and results from inappropriate immune responses to inhaled allergens leading to airway inflammation, excessive mucus production, and bronchial airway hyperresponsiveness (AHR). Impaired efferocytosis has been observed in asthmatics, and defects in efferocytosis are associated with increased risk or severity of asthma. Therapeutics that promote efferocytosis are promising candidates for the treatment of asthma, in which certain endotypes present unmet medical needs. [ABSTRACT FROM AUTHOR]