Marco Colonna, MD
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 human 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-g, have a unique location at the intraepithelial interface and are likely to play an important role in gastrointestinal immune responses  . Currently, we are profiling the transcriptome of ILCs in collaboration with the ImmGen consortium. We are also investigating the role of Notch and aryl hydrocarbon receptor (AHR) in ILC development as well as developing mouse models lacking ILC subsets to understand their functions in infections and inflammatory bowel disease.
2) Plasmacytoid dendritic cells and IFNa/b 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. IFNa/b. We described pDCs in 1999 as the professional IFNa/b-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 IFNa, we are currently 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. We also recently demonstrated that the cytokine IL-34 promotes the proliferation and survival of microglia through the receptor CSF-1R  . We are testing IL-34 as a therapeutic strategy for neurodegenerative diseases.
- Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JK, Doherty JM, Mills JC, Colonna M: A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 2009, 457:722-725.
- Fuchs A, Vermi W, Lee JS, Lonardi S, Gilfillan S, Newberry RD, Cella M, Colonna M: Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-gamma-producing cells. Immunity 2013, 38:769-781.
- Cella M, Jarrossay D, Facchetti F, Alebardi O, Nakajima H, Lanzavecchia A, Colonna M: Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med 1999, 5:919-923.
- Swiecki M, Gilfillan S, Vermi W, Wang Y, Colonna M: Plasmacytoid dendritic cell ablation impacts early interferon responses and antiviral NK and CD8(+) T cell accrual. Immunity 2010, 33:955-966.
- Wang Y, Swiecki M, McCartney SA, Colonna M: dsRNA sensors and plasmacytoid dendritic cells in host defense and autoimmunity. Immunol Rev 2011, 243:74-90.
- Klesney-Tait J, Turnbull IR, Colonna M: The TREM receptor family and signal integration. Nat Immunol 2006, 7:1266-1273.
- Wang Y, Szretter KJ, Vermi W, Gilfillan S, Rossini C, Cella M, Barrow AD, Diamond MS, Colonna M: IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat Immunol 2012, 13:753-760.
DBBS Graduate Program Affiliation
Arifumi Iwata, MD, PhD
|Maristela Hernandez||Isaiah Turnbull|
|Axel Bouchon||Jacob Lee||Yaming Wang|
|Cecilia Buonsanti||Steve McCartney||Timothy Wilson|
|Anja Fuchs||Aaron Rapaport|
|Anne Krug||Sarah Rowland|
|Gaelle Le Friec||Melissa Swiecki|
|Jes Dietrich||Hideo Nakajima||Ilaria Tassi|
|Leonid Gitlin||Karel Otero||Yoshinori Yamanishi|
|Izumi Kawachi||Laura Piccio|
|Julia Klesney-Tait||Rachel Presti|