Dr. Marco Colonna was born in Parma, Italy, received his medical degree and specialization in internal medicine at Parma University (Parma, Italy) and completed his postdoctoral training at Harvard Medical School (Cambridge, Massachusetts, USA). He became a scientific member of the Basel Institute for Immunology (Basel, Switzerland). Since 2001 he has been a Professor of Pathology & Immunology at Washington University School of Medicine in St. Louis, MO, USA. Dr. Colonna’s research focuses on immunoreceptors. In this field his accomplishments encompass identification and characterization of the Killer cell Ig-like receptors and HLA-C polymorphisms as their inhibitory ligands, as well as the discovery of the LILR and TREM inhibitory and activating receptor families. Through analysis of the cellular distribution of these receptors, he identified plasmacytoid dendritic cells as source of IFN alfa/beta in anti-viral responses and innate lymphoid cells that produce IL-22 in mucosae. His current areas of research include: 1) Innate lymphoid cells in mucosal immunity. 2) Plasmacytoid dendritic cells in host defense and autoimmunity. 3) TREM2 and innate immunoreceptors in Alzheimer’s disease.

Research Interests

My laboratory is broadly interested in innate immunity, focused in three main areas:
1) Innate lymphoid cells (ILCs) in mucosal immunity
The laboratory has a long-standing interest in ILCs, which are lymphocytes that lack specific antigen receptors. They are found in the mucosae and mucosal-associated lymphoid tissues, where they promptly initiate cytokine responses to pathogens. In 2008 we identified, in humans and mice, a subset of ILCs that produce IL-22 in response to IL-23. These cells, which are now known as ILC3, are a critical component of mucosal immune responses in health and disease. Recently, we identified a second subset of mucosal ILC that produce IFN-gamma, have a unique location at the intraepithelial interface and are likely to play an important role in gastrointestinal immune responses. Currently, we have profiled the ILC transcriptome in collaboration with the ImmGen consortium, and we are currently investigating ILC heterogeneity by single cell RNA seq and ILC epigenetic regulation. We have also developed mouse models lacking ILC subsets to understand their functions in infections and inflammatory bowel disease.
2) Plasmacytoid dendritic cells and IFN-alpha/beta in host defense and autoimmunity
Plasmacytoid dendritic cells (pDCs) are bone marrow-derived leukocytes that detect RNA and DNA from viruses and RNA/DNA/immunocomplexes through two endosomal sensors, TLR7 and TLR9, and secrete large amounts of type I interferons, i.e. IFNalpha/beta. We described pDCs in 1999 as the professional IFN-alpha/beta-producing cells in response to influenza virus in human blood and contributed numerous observations to the field of pDC research. Recently, we developed a transgenic mouse model where pDCs can be specifically ablated for long periods of times. By using this tool we have addressed the relevance of pDCs in infections compared to other anti-viral mechanisms. Because autoimmune diseases, such as Systemic lupus erythematosus (SLE), are associated with excessive pDC activation and secretion of IFN-alpha, we are exploring the impact of pDCs on models of SLE and testing whether disabling pDCs is a viable therapeutic strategy that can be applied to human autoimmune diseases.
3) Innate immune mechanisms in Alzheimer?s disease and neurodegeneration
Triggering receptors expressed on myeloid cells (TREM) are cell surface receptors encoded on human chromosome 6 that we found to be differentially expressed on granulocytes, dendritic cells, macrophages and osteoclasts and regulate their functions. Human deficiency in TREM2 or the associated signaling adaptor DAP12 causes a progressive, early onset dementia known as Nasu-Hakola disease. Recently, a TREM2 polymorphism was implicated as a genetic risk for Alzheimer?s disease (AD). We are currently exploring the capacity of TREM2 to promote microglial cell function and how TREM2 allelic variants result in susceptibility to AD.

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Section 43: Immunology and Inflammation