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The homeostasis and health of an organism depend on the coordinated interaction of specialized organs, which is regulated by interorgan communication networks of circulating soluble molecules and neuronal connections. Many diseases that seemingly affect one primary organ are really multiorgan diseases, with substantial secondary remote organ complications that underlie a large part of their morbidity and mortality. Acute kidney injury (AKI) frequently occurs in critically ill patients with multiorgan failure and is associated with high mortality, particularly when it occurs together with respiratory failure. Inflammatory lung lesions in patients with kidney failure that could be distinguished from pulmonary oedema due to volume overload were first reported in the 1930s, but have been largely overlooked in clinical settings. A series of studies over the past two decades have elucidated acute and chronic kidney–lung and lung–kidney interorgan communication networks involving various circulating inflammatory cytokines and chemokines, metabolites, uraemic toxins, immune cells and neuro-immune pathways. Further investigations are warranted to understand these clinical entities of high morbidity and mortality, and to develop effective treatments. Here, the authors review the current understanding of interorgan crosstalk mechanisms, with a focus on interorgan communication in the kidney–lung axis during acute or chronic disease of the kidney or lung. Key points: Interorgan communication networks consist of soluble circulating factors, the immune system and the nervous system, and involve neuro-immune and neuro-endocrine interactions. Acute kidney injury (AKI) causes long-recognized complications, such as uraemia and volume overload, and less well understood "non-traditional" complications, such as remote organ dysfunction and immune dysfunction, which contribute to increased morbidity and mortality. AKI-induced remote lung inflammation depends on the actions of soluble circulating factors that are released by the kidney and other organs, including osteopontin, HMGB1, IL-6, IL-8 and TNF, and of immune cells, including neutrophils, monocytes, macrophages and T cells. Primary lung injury due to infection, acid aspiration, ischaemia–reperfusion injury or barotrauma can lead to AKI in rodents and humans; some of the mechanisms of lung–kidney crosstalk are similar to those implicated in kidney–lung crosstalk, but more mechanistic studies are required. Studies in preclinical models and correlative evidence from clinical studies suggest a bidirectional detrimental relationship between chronic kidney disease and chronic lung disease; however, the molecular mechanisms are largely unknown. [ABSTRACT FROM AUTHOR]

Ischemia/reperfusion injury-mediated (IRI-mediated) primary graft dysfunction (PGD) adversely affects both short- and long-term outcomes after lung transplantation, a procedure that remains the only treatment option for patients suffering from end-stage respiratory failure. While B cells are known to regulate adaptive immune responses, their role in lung IRI is not well understood. Here, we demonstrated by intravital imaging that B cells are rapidly recruited to injured lungs, where they extravasate into the parenchyma. Using hilar clamping and transplant models, we observed that lung-infiltrating B cells produce the monocyte chemokine CCL7 in a TLR4-TRIF-dependent fashion, a critical step contributing to classical monocyte (CM) recruitment and subsequent neutrophil extravasation, resulting in worse lung function. We found that synergistic BCR-TLR4 activation on B cells is required for the recruitment of CMs to the injured lung. Finally, we corroborated our findings in reperfused human lungs, in which we observed a correlation between B cell infiltration and CM recruitment after transplantation. This study describes a role for B cells as critical orchestrators of lung IRI. As B cells can be depleted with currently available agents, our study provides a rationale for clinical trials investigating B cell-targeting therapies. [ABSTRACT FROM AUTHOR]