Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation

Ignacio J. Juncadella et al., Nature 493, 547–551 (24 January 2013)

Speaker: Nai-Huei Jhong (鍾乃惠)                               Time:13:00~14:00,March.27, 2013

Commentator: Dr. Jiu-Yao Wang(王志堯 老師)         Place: Room 601

Abstract

The airway epithelium is the first barrier of defense including environmental pollutants, allergens and pathogens in the lung. Airway epithelial cells can undergo apoptosis to reduce the damage of allergy and infection¹. The mechanism and effect of apoptotic cell clearance in airway inflammation remain poorly understood. It has been known that in addition to professional phagocytes such as macrophages and dendritic cells, the lung contains nonprofessional phagocytes to maintain airway clearance². However, airway epithelial cells greatly outnumber professional phagocytes. In this paper, the authors investigated whether epithelial cells can clear apoptotic cells from the airways. They targeted the small GTPase Rac1, which regulates cytoskeleton of cell engulfment. Deletion of Rac1 expression specifically in airway epithelial cells in mice resulted in defective engulfment by epithelial cells and aberrant anti-inflammatory cytokine production. Intranasal priming and challenge of these mice with house dust mite extract (HDM) or ovalbumin (OVA) as allergens led to exacerbated inflammation, enhanced Th2 cytokines and airway hyper-responsiveness, with decreased interleukin 10 (IL-10) in bronchial lavages. Rac1-deficient epithelial cells produced higher IL-33 upon allergen or apoptotic cell encounter, with increased numbers of IL-5⁺ group 2 innate lymphoid cells (nuocyte-like cells). Administration of exogenous IL-10 decreased the IL-33 amounts in the BAL fluid and reduced airway inflammation phenotype in Rac1-deficient mice. Collectively, this study suggests that airway epithelial cells can be phagocytic, and secrete/modulate cytokines to tolerate common airway allergens.

References

1.          Jyonouchi, H., et al., Airway epithelium and apoptosis. Apoptosis 4, 407–417 (1999).

2.          Monks, J. et al., Epithelial cells as phagocytes: apoptotic epithelial cells are engulfed by mammary alveolar epithelial cells and repress inflammatory mediator release. Cell Death Differ. 12, 107–114 (2005).