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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

Clinical benefits of reperfusion after myocardial infarction are offset by maladaptive innate immune cell function, and therapeutic interventions are lacking.

MerTK Cleavage on Resident Cardiac Macrophages Compromises Repair After Myocardial Ischemia Reperfusion Injury.

Our data suggest that, after a myocardial infarction, integrin-associated protein CD47 on cardiac myocytes is elevated. In culture, increased CD47 on the surface of dying cardiomyocytes impairs phagocytic removal by immune cell macrophages. After myocardial ischemia and reperfusion, acute CD47 inhibition with blocking antibodies enhanced dead myocyte clearance by cardiac phagocytes and also improved the resolution of cardiac inflammation, reduced infarct size, and preserved cardiac contractile function. Early targeting of CD47 in the myocardium after reperfusion may be a new strategy to enhance wound repair in the ischemic heart.

Acute CD47 Blockade During Ischemic Myocardial Reperfusion Enhances Phagocytosis-Associated Cardiac Repair.

Post-transplant immunosuppression has reduced the incidence of T cell-mediated acute rejection, yet long-term cardiac graft survival rates remain a challenge. An important determinant of chronic solid organ allograft complication is accelerated vascular disease of the transplanted graft. In the case of cardiac allograft vasculopathy (CAV), the precise cellular etiology remains inadequately understood; however, histologic evidence hints at the accumulation and activation of innate phagocytes as a causal contributing factor. This includes monocytes, macrophages, and immature dendritic cell subsets. In addition to crosstalk with adaptive T and B immune cells, myeloid phagocytes secrete paracrine signals that directly activate fibroblasts and vascular smooth muscle cells, both of which contribute to fibrous intimal thickening. Though maladaptive phagocyte functions may promote CAV, directed modulation of myeloid cell function, at the molecular level, holds promise for tolerance and prolonged cardiac graft function.

Article	Year
MerTK Cleavage on Resident Cardiac Macrophages Compromises Repair After Myocardial Ischemia Reperfusion Injury. Circulation research\| PubMed ID: 28851810	2017
Acute CD47 Blockade During Ischemic Myocardial Reperfusion Enhances Phagocytosis-Associated Cardiac Repair. JACC. Basic to translational science\| PubMed ID: 28920097	2017
Acute and chronic phagocyte determinants of cardiac allograft vasculopathy. Seminars in immunopathology\| PubMed ID: 30141073	2018

Xin Yi Yeap

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