a-mouse-model-vascularized-heterotopic-spleen-transplantation-for

A Mouse Model of Vascularized Heterotopic Spleen Transplantation for Studying Spleen Cell Biology and Transplant Immunity

The spleen is a unique lymphoid organ that plays a critical role in the homeostasis of the immune and hematopoietic systems. Patients that have undergone ...

Northwestern University

Ischemia-reperfusion injury, a form of sterile inflammation, is the leading risk factor for both short-term mortality following pulmonary transplantation and chronic lung allograft dysfunction. While it is well recognized that neutrophils are critical mediators of acute lung injury, processes that guide their entry into pulmonary tissue are not well understood. Here, we found that CCR2+ classical monocytes are necessary and sufficient for mediating extravasation of neutrophils into pulmonary tissue during ischemia-reperfusion injury following hilar clamping or lung transplantation. The classical monocytes were mobilized from the host spleen, and splenectomy attenuated the recruitment of classical monocytes as well as the entry of neutrophils into injured lung tissue, which was associated with improved graft function. Neutrophil extravasation was mediated by MyD88-dependent IL-1β production by graft-infiltrating classical monocytes, which downregulated the expression of the tight junction-associated protein ZO-2 in pulmonary vascular endothelial cells. Thus, we have uncovered a crucial role for classical monocytes, mobilized from the spleen, in mediating neutrophil extravasation, with potential implications for targeting of recipient classical monocytes to ameliorate pulmonary ischemia-reperfusion injury in the clinic.

Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1β.

Cytomegalovirus (CMV) infection has been associated with poor outcomes after solid organ transplantation. The long-term impact of donor and recipient CMV serological status on lung transplant outcomes remains unclear. Accordingly, we evaluated the impact of donor and recipient CMV status on long-term patients as well as allograft survival after single (SLT) and double lung transplantation (BLT).

Long-Term Impact of Cytomegalovirus Serologic Status on Lung Transplantation in the United States.

The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual cell populations during pulmonary fibrosis that are important for disease pathogenesis.

Article	Year
Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1β. The Journal of clinical investigation\| PubMed ID: 29781811	2018
Long-Term Impact of Cytomegalovirus Serologic Status on Lung Transplantation in the United States. The Annals of thoracic surgery\| PubMed ID: 30476471	2019
Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis. American journal of respiratory and critical care medicine\| PubMed ID: 30554520	2018

Ramiro Fernandez

Biography

JoVE Journal Publications

Other Publications