ABSTRACT
Pericytes have been implicated in lung injury and repair in a number of organs. Our research focuses on the
role of lung stromal subpopulations in tissue injury and repair, and our recent work revealed lung pericytes
may have multiple functional roles during injury. Data from transcriptomic analyses of activated lung
pericytes reveal upregulation of multiple genes involved in inflammation, angiogenesis, and matrix
remodeling. The goal of this project is to characterize the functional diversity of pericytes in their response
to a clinically relevant model of lung injury – influenza infection. To achieve this goal, we will test
hypotheses on the roles of pericytes in endothelial and immune regulation. In Aim 1, we will investigate the
mechanisms of pericyte-endothelial cell crosstalk that lead to activation of endothelial cells and increased
lung permeability. Angiopoietin-L4 (ANGPTL4) has been implicated as a hyperpermeability factor that is
also highly upregulated in activated lung pericytes in our preliminary studies. We will examine how pericyte-
derived ANGPTL4 affects lung endothelial function in this aim. In Aim 2, we will evaluate the role of lung
pericytes in trafficking inflammatory monocytes. In murine models of influenza infection, inflammatory
monocytes have been implicated in the development of lung injury. Recruitment of inflammatory monocytes
in influenza occurs through a CC-chemokine receptor 2 (CCR2) dependent mechanism. Our work shows
that activated pericytes highly upregulate CCL2, a major ligand for CCR2. We will evaluate the functional
role of pericyte-derived CCL2, and other CCR2 ligands, in inflammatory monocyte recruitment. Finally, in
Aim 3, we will characterize functional subsets in the pericyte population using single nucleus transcriptomic
approaches. This proposed aim will provide insight into the diverse functional states of lung pericytes
throughout the course of influenza infection and functional subtypes that mediate lung injury.