Authorship note: KJL and DK are co-senior authors. Conflict of interest: DK serves on The Scientific Advisory Board of and receives research support from Compass Therapeutics. DK and KJL have a pending patent entitled "Compositions and methods for detecting CCR2 receptors" (US patent application no. 15/611,577).

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Significance Intravital imaging, oxidative lipidomics, and a transplant model were used to define mechanisms that regulate neutrophil recruitment into lungs during ischemia reperfusion injury, a clinically relevant form of sterile inflammation. We found that early neutrophil-mediated damage is largely confined to the subpleural vasculature, a process that is orchestrated by a spatially restricted distribution of nonclassical monocytes that produce chemokines following necroptosis of pulmonary cells. Neutrophils disrupt the integrity of subpleural capillaries, which is associated with impaired lung function. Neutrophil-mediated vascular leakage is dependent on TLR4 expression on vascular endothelium, NOX4 signaling, and formation of neutrophil extracellular traps. Our research provides insights into mechanisms that regulate neutrophil recruitment during sterile lung inflammation and lays the foundation for developing new therapies.

The majority of dialysis-dependent patients undergoing valve replacement have poor survival. Given that survival is short, biological valves may be the more appropriate choice in most patients.

Chronic lung allograft dysfunction (CLAD) encompasses a range of pathologies that cause a transplanted lung to not achieve or maintain normal function. CLAD manifests as airflow restriction and/or obstruction and is predominantly a result of chronic rejection. Three distinct phenotypes of chronic rejection are now recognized: bronchiolitis obliterans, neutrophilic reversible allograft dysfunction, and restrictive allograft syndrome. Recent investigations have revealed that each phenotype has a unique pathology and histopathological findings, suggesting that treatment regimens should be tailored to the underlying etiology. CLAD is poorly responsive to treatment once diagnosed, and therefore the prevention of the factors that predispose a patient to develop CLAD is critically important. Small and large animal models have contributed significantly to our understanding of CLAD and more studies are needed to develop treatment regimens that are effective in humans.

| INTRODUC TI ONBronchus-associated lymphoid tissue (BALT) is a pulmonary tertiary lymphoid organ (TLO) that plays a critical role in the inflammatory response to a range of lung pathology, including infection, autoimmunity, and allograft rejection. 1-3 However, recent evidence has emerged that pulmonary TLOs are not synonymous with the generation of deleterious proinflammatory responses. [4][5][6][7] To this end, the development of BALT has been associated with the downregulation of immune responses. Tumor-associated TLOs are one such example, which have been found in both human and mouse models of lung cancer. 4 Pulmonary tumor-associated TLOs are enriched in Foxp3 + regulatory T contributed equally to this manuscript and share first authorship Abbreviations: AHR, aryl hydrocarbon receptor; BALT, bronchus-associated lymphoid tissue; H&E, hematoxylin and eosin; HEV, high endothelial venule; ILC, innate lymphoid cell; NALT, nasal-associated lymphoid tissue; PNAd, peripheral nodal addressin; RORγt, retinoic acid receptor-related orphan receptor gamma t; SLO, secondary lymphoid organ; TLO, tertiary lymphoid organ; γδ, gamma-delta. Long-term survival after lung transplantation remains profoundly limited by graft rejection. Recent work has shown that bronchus-associated lymphoid tissue (BALT), characterized by the development of peripheral nodal addressin (PNAd)-expressing high endothelial venules and enriched in B and Foxp3 + T cells, is important for the maintenance of allograft tolerance. Mechanisms underlying BALT induction in tolerant pulmonary allografts, however, remain poorly understood. Here, we show that the development of PNAd-expressing high endothelial venules within intragraft lymphoid follicles and the recruitment of B cells, but not Foxp3 + cells depends on IL-22. We identify graft-infiltrating gamma-delta (γδ) T cells and Type 3 innate lymphoid cells (ILC3s) as important producers of IL-22. Reconstitution of IL-22 at late time points through retransplantation into wildtype hosts mediates B cell recruitment into lymphoid follicles within the allograft, resulting in a significant increase in their size, but does not induce PNAd expression. Our work has identified cellular and molecular requirements for the induction of BALT in pulmonary allografts during tolerance induction and may provide a platform for the development of new therapies for lung transplant patients. K E Y W O R D S animal models: murine, basic (laboratory) research/science, immunobiology, lung transplantation/pulmonology, lymph node, lymphocyte biology, tolerance: experimental

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Outcomes after lung transplant lag behind those of other solid-organ transplants. A better understanding of the pathways that contribute to rejection and tolerance after lung transplant will be required to develop new therapeutic strategies that take into account the unique immunological features of lungs. Mechanistic immunological investigations in an orthotopic transplant model in the mouse have shed new light on immune responses after lung transplant. Here, we highlight that interactions between immune cells within pulmonary grafts shape their fate. These observations set lungs apart from other organs and help provide the conceptual framework for the development of lung-specific immunosuppression.