Research Abstract:
My laboratory studies the function of natural killer (NK) cells, dendritic cells (DC) and plasmacytoid dendritic cells (PDC), also known as natural interferon-producing cells (IPC), in innate immune responses.
NK cell, DC and PDC effector functions are regulated by a balance of activating and inhibitory signals transduced by a variety of distinct receptors. Our previous accomplishments in this field include identifying the human killer cell immunoglobulin-like receptors (KIRs) and characterizing HLA-C polymorphisms that serve as their inhibitory ligands. We also discovered the leukocyte immunoglobulin-like receptors (LILRs) as well as inhibitory and activating receptors that belong to the triggering receptors expressed by myeloid cells (TREM) family. We are actively pursuing identification of TREM ligands, the role of TREM-1 in sepsis and the function of TREM-2 in development of dendritic cells, microglia and osteoclasts. In addition, we are studying signaling of NK cell, DC and PDC activating receptors through the signaling adapters DAP10 and DAP12.
PDC are bone marrow derived cells that specialize in the secretion of IFN-α and IFN-β in response to DNA and RNA viruses. We demonstrated that PDC secrete IFN-α, induce Th1 polarization of T cell responses and, hence, are equivalent to IPC. Presently, we are assessing the function of PDC during immune responses to infections caused by ssRNA viruses (Influenza) and DNA viruses (HSV-1 and MCMV). Finally, we are determining which adhesion molecules and chemokines regulate the migration of PDC from the blood through high endothelial venules into the lymph nodes during immune responses.
Selected Publications:
Cella M, Buonsanti C, Strader C, et al. Impaired differentiation of osteoclasts in TREM-2-deficient individuals. J Exp Med 2003 198:645-651.
Colonna M. TREMs in the immune system and beyond. Nat Rev Immunol 2003 3:445-453.
Colonna M, Krug A, Cella M. Interferon-producing cells: On the front line in immune responses against pathogens. Curr Opin Immunol 2002 14:373-379.
Gilfillan S, Ho EL, Cella M, Yokoyama WM, Colonna M. NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation. Nat Immunol 2002 3:1150-1155.
Bouchon A, Facchetti F, Weigand MA, Colonna M. TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature 2001 410:1103-1107.
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