Contribution of Mononuclear Phagocyte Lineage to Tissue Immunity and Homeostasis

The mononuclear phagocyte system (MPS) includes monocytes, macrophages and dendritic cells (DC). Tissue phagocytes share a unique ability to sample environmental antigens, sense and respond to tissue injuries, and shape immune responses to pathogens that breach the tissues. Mononuclear phagocytes play a critical role in maintaining organismal homeostasis and their activities are relevant in inflammation, autoimmunity, infection, cancer and organ transplant.

What is becoming increasingly clear is that monocytes, macrophages and DCs are not homogenous populations. Just as CD4+ T cells further differentiate into distinct subsets, such as TH1, TH2, TH17 and T-regulatory cells, so do monocytes, macrophages, and DCs. Although several subsets of monocytes, macrophages and DCs have been identified, the individual contributions of these subsets to health and disease is not well known. It is probable that additional, functionally distinct subsets exist. Moreover, few of the relevant genes involved in the development and function of MPS cells have been characterized. The mission of our laboratory is to fill this gap of knowledge by studying the mechanisms that regulate the ontogeny homeostasis of mononuclear phagocytes in interface tissues, in both mice and humans.

Our group also focuses on studying the contributions of DC and macrophages, especially in lung, gut and skin immunity. In the lung, we study the diversity of lung DC populations and their role in influenza virus immunity. In the gut, we study the role of mononuclear phagocytes in the maintenance of tissue integrity and in the developemnt of colitis, whereas in the skin, we study the dynamics of epidermal and dermal DC in the steady state and in different inflammed state.