The active role of pulmonary immunity in ischaemic stroke

Previous stroke studies have mostly regarded the lungs as passively damaged target organs, and in clinical practice in the context of stroke, the role of the lungs has been habitually limited to secondary complications such as stroke-associated pneumonia or neurogenic pulmonary oedema. However, recent studies have indicated that the lung plays a more active and central role in the pathophysiology of stroke. In this review, we propose and systematically elaborate on an emerging concept: the lung, as one of the largest immune organs in the body, functions as an active initiator and amplifier of systemic inflammation and neuroinflammation following stroke. Stroke "remotely primes" the unique immune reservoir of the lung (such as marginated pool neutrophils and resident macrophages) via neural and humoral pathways, leading to the rapid activation and release of these cells into the circulation. Activated pulmonary immune cells not only possess an enhanced capacity for brain homing but also produce large amounts of proinflammatory mediators, establishing a self-amplifying inflammatory cycle that significantly worsens neurological outcomes. Furthermore, we explore how advanced age and metabolic comorbidities, such as diabetes, pathologically remodel the pulmonary immune baseline, thereby increasing susceptibility to this self-amplifying cascade. By highlighting the current translational gap between preclinical models and human clinical cohorts, we propose that elevating the lung from a therapeutic bystander to a core intervention target provides a novel "brain-lung coprotection" strategy, which may offer a new perspective for optimizing the comprehensive clinical management of ischaemic stroke.