Unveiling lung resilience mechanisms: a ground-breaking way to cope with air pollution

Air pollution, exacerbated by heatwaves and wildfires, affects primarily the lungs, leading to potentially life-threatening effects eluding conventional treatments.

In response, KINTSUGI adopts a new perspective by exploring lung resilience mechanisms, to understand how respiratory health is maintained in most individuals: drawing on evidence from both a broad evolutionary standpoint, where humans have evolved in environments exposed to particles and proofs of lung resilience observed particularly in smokers, it seeks to redefine the paradigm of investigating lung response to particulate pollution.For that, KINTSUGI focuses on the airway submucosal gland (SMG), an ectodermal appendage lining the airways, renowned for its unique properties in mucus secretion, antimicrobial activity and a potential niche for proximal airway stem cells.

The hypothesis posits the airway SMG as a crucial signalling hub, orchestrating responses to external perturbations to ensure proximal lung resilience.

Using dissected clinical samples of SMG, it aims to unravel cell interactions intricacies within this niche, ultimately generating a ""SMG-related resilience signature"".

Additionally, 3D in vitro models replicating the in vivo architecture and function of airway SMGs will be established for the study of mucociliary clearance, antimicrobial activity, and regeneration studies under both homeostatic conditions and particles exposure.

KINTSUGI further integrates probabilistic mathematical modelling, considering microscopic interaction rules within the SMG, to elucidate macroscopic behaviours underlying lung resilience at different time scales.KINTSUGI anticipates impacting broader scientific communities, as such health, biology, and evolution, by uncovering fundamental insights into the mechanisms governing resilience.

The impact on health and its potential to resonate across diverse scientific disciplines positions KINTSUGI as a ground-breaking initiative with far-reaching implications.