Role of human monocytes in lung injury and inflammation

The immune system can protect against infection, but inflammatory immune responses can also cause organ damage in many lung diseases.

Specialized immune cells, monocytes, contribute to lung injury in severe respiratory infections and chronic inflammatory lung diseases.

With help of previous VR funding, we discovered how blood monocytes generate human lung macrophages (Immunity 2021) and how cell origin determines their function (J Exp Med 2022).

Following up on these seminal discoveries, we now investigate monocytes in virus infection and immune-mediated lung injury using a unique in-vivo model of human lung immunity that I developed (Nature Biotechnology 2014).

Our specific aims are: (1) Determine how blood monocytes migrate into the inflamed lung after virus infection; (2) Define the role of recruited versus resident human monocytes in lung injury; (3) Examine the function of newly discovered GPR183-monocytes in the injured lung that respond to inflammatory cholesterol metabolites, which connects to our previous work on oxysterols (Immunity 2018).To achieve these aims, we will perform in-vivo studies with human immune system mice combined with advanced immunological and system biology approaches.

This project will provide important knowledge on how the immune system promotes lung injury and could indicate new ways of ameliorating the damaging effects of inflammatory immune responses in many common lung diseases.