Research

Barrier tissues like the lungs, skin, and the gut are lined by layer/s of epithelial cells that act as a direct interface between the core of the body and the external environment (Fig 1A). This implies recurrent and inevitable bombardment of these cells by different microbes (innocuous commensals, and pathogens), environmental insults (like smoke, corrosives, allergens, physical stressors, etc) and potentially tumorigenic cells as we age (Fig 1B). Thus, to ensure host survival, barrier epithelial cells have to sense these insults and rapidly eliminate them (using intrinsic mechanisms conferred by innate immunity and by recruiting other immune cells)(Fig 1B). Once these insults are cleared, the epithelium also has to engage appropriate stem cell reservoirs to repair the injury optimally so that the barrier tissue (and hence the host) can live to fight (better and faster) on another day (Fig 1B). Failure at any of these steps can lead to catastrophic consequences for the tissue in question (Fig 2). It is awe-inspiring that despite the plethora of potentially life-threatening insults that we face on a daily basis, evolution has forged us a barrier tissue system that confers us with abilities to resist these insults and recover from them in an iteratively improved fashion.

A prime example of such a malleable and effective barrier tissue system is the lung and their epithelial cells. An average human adult breathes in ~11,000 liters of air on a daily basis wherein each breath is distributed over an epithelial surface area equivalent to a tennis court and each bout of this "life-giving" gas exchange happens across an alveolar epithelial-capillary barrier which is less than 1micron thick. Thus, lung epithelial cells have to eliminate airborne agents as they pass down the airway tree to ensure near sterility of the air reaching the alveoli for gas exchange with the circulatory system. To do so, we have evolved an intricate system where distinct lung epithelial and stem cells occupying discrete niches within the mammalian lungs not only act as physical barriers and innate effector cells (by producing mucus, detoxifying enzymes, surfactants, and antimicrobial peptides, etc) but also communicate with neighboring structural and immune (innate and adaptive) cells to program a well regulated immune and tissue repair response as part of pulmonary immunity.