Our work focuses on identifying and characterizing the cells that regulate immune-mediated diseases.
Specific interests include:
- Chemokines, a family of small proteins that stimulate the migration of inflammatory cells
- Dendritic cells, which function in both the initiation and regulation of immune response
- Inflammatory monocytes, which mediate several types of inflammation
We are currently working to characterize immune cells in blood vessels and lungs to understand how processes such as atherosclerosis, pulmonary sensitization to airborne antigens, and influenza-induced lung injury occur.
Atherosclerosis is an immune-mediated disease in which innate, T cell, and B cell immune responses are required for disease initiation and progression. We have identified a population of dendritic cells within the intima of mouse arteries that are present only in regions in which atherosclerosis will develop.
We are now determining the role of these cells in the development of atherosclerosis and the associated immune responses. These experiments will, for the first time, directly test the hypothesis that dendritic cells regulate the development of atherosclerosis and will elucidate the function of individual cell types in vascular disease.
In a separate project, we have characterized the inflammatory cells that arise in the lungs during influenza infection and identified those cells that cause the lung injury that leads to acute respiratory distress syndrome (ARDS). We are now testing strategies to inhibit this damage and thereby improve the survival of patients with ARDS or infected with highly pathogenic avian influenza virus.
- Gunn MD, Nelken NA, Liao X, Williams LT. Monocyte chemoattractant protein-1 is sufficient for the chemotaxis of monocytes and lymphocytes in transgenic mice but requires an additional stimulus for inflammatory activation. J Immunology 158: 376, 1997.
- Gunn MD, Tangemann K, Tam C, Cyster JG, Rosen SD, Williams LT. A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes. Proc Nat Acad Sci 95: 258, 1998.
- Gunn MD, Ngo V, Ansel M, Ekland E, Cyster JG, Williams LT. A B-cell homing chemokine made in lymphoid follicles activates the BLR1 receptor.Nature 391: 799, 1998.
- Gunn MD, Kyuwa S, Tam C, Kakiuchi T, Matsuzawa A, Williams LT, Nakano H. Mice lacking expression of secondary lymphoid-organ chemokine have defects in lymphocyte homing and dendritic cell localization. J Exp Med189: 451, 1999.
- Nakano H, Yanagita M, Gunn MD. CD11c+ B220+ Gr-1+ cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells. J Exp Med 194: 1171, 2001.
Michael D. Gunn, MD, Director
Office: 346 Sands Building, Durham, NC, 27710
Campus mail: DUMC Box 3547, Durham, NC, 27710