Durham, NC 27710
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Immunologic aspects of cardiovascular diseases
The focus of our work is on understanding how dendritic cells and other myeloid cells initiate and regulate immune responses. We are also using our knowledge of immunology to develop diagnostics and therapeutics for a variety of human diseases.
The lab started with our discovery of the lymphoid chemokines, which regulate the migration of lymphocytes and dendritic cells to and within secondary lymphoid organs. We identified CCL21 as the chemokine that mediates the entry of naïve T cells and dendritic cells into lymph nodes. We identified CXCL13 as the chemokine that mediates the entry of B cells into lymphoid follicles. We determined that the murine plt mutation is due to a loss of CCL21 expression in lymphoid organs and that this leads to major defects in dendritic cell migration.
Our focus then shifted to understanding how specific cell types, primarily dendritic cells, and cell migration events regulate immune responses. We identified both murine plasmacytoid dendritic cells and the dendritic cell subset that stimulates Th1 immune responses. Our current work continues these basic studies while applying our findings to models of human disease.
Understanding how dendritic cells regulate the strength, duration, and character of immune response – Lymph nodes contain six distinct DC populations, including inflammatory monocyte-derived dendritic cells. Through the use of extensive flow cytometric analysis and chemokine-deficient mice, we are determining how these DC populations act to regulate innate and adaptive immune responses. Once these pathways are defined in model systems, we examine how they contribute to the pathophysiology of specific infections and diseases.
Mechanisms of pulmonary immune pathology – Using the techniques we developed to characterize lymph node DC subsets, we identified the lung inflammatory cell type that causes pulmonary immune pathology during influenza infection. We are currently examining the role that specific inflammatory cells and mediators play in other types of respiratory dysfunction such as chemical-induced Acute Lung Injury and Bronchiolitis Obliterans. We have an active program to develop therapeutics for these disorders.
Regulation of vascular remodeling by myeloid cells – Inflammation is closely associated with the growth and remodeling of blood vessels. Using methods that allow the targeting of specific myeloid cell populations, we are examining the contribution of these cells to vascular growth and remodeling in a number of disease models.
Development of recombinant antibodies as diagnostic reagents – Our lab has developed novel methods to generate recombinant single chain antibodies using phage display technology. We are currently using these methods to generate pathogen-specific antibodies for use in diagnostic tests for a variety of human bacterial and fungal infections. To date, our approach has been extremely successful and we anticipate commercialization of at least one diagnostic test in the near future. We are currently seeking collaborators with expertise in specific infectious diseases to expand our diagnostics program to other pathogens.
This faculty member has no reported relationships with industry.
Liang, J; Jung, Y; Tighe, RM; Xie, T; Liu, N; Leonard, M; Gunn, MD; Jiang, D; Noble, PW. A macrophage subpopulation recruited by CC chemokine ligand-2 clears apoptotic cells in noninfectious lung injury. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2012;302:L933-L940. (2012) Abstract
Cain, DW; Gunn, MD. NUR who? An orphan transcription factor holds promise for monomaniacs. Nature Immunology. 2011;12:727-729. (2011) Abstract
Lin, KL; Sweeney, S; Kang, BD; Ramsburg, E; Gunn, MD. CCR2-antagonist prophylaxis reduces pulmonary immune pathology and markedly improves survival during influenza infection. Journal of Immunology. 2011;186:508-515. (2011) Abstract
Chen, YH; Lipes, BD; Kenan, DJ; Staats, HF; Gunn, MD. Identification of recombinant antibodies against multiple distinct toll-like receptors by homolog mining a single immune scFv phage library. Journal of Immunological Methods. 2009;340:144-153. (2009) Abstract
Nakano, H; Lin, KL; Yanagita, M; Charbonneau, C; Cook, DN; Kakiuchi, T; Gunn, MD. Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responses. Nature Immunology. 2009;10:394-402. (2009) Abstract
Lin, KL; Suzuki, Y; Nakano, H; Ramsburg, E; Gunn, MD. CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality. Journal of Immunology. 2008;180:2562-2572. (2008) Abstract
Lipes, BD; Chen, YH; Ma, H; Staats, HF; Kenan, DJ; Gunn, MD. An entirely cell-based system to generate single-chain antibodies against cell surface receptors. Journal of Molecular Biology. 2008;379:261-272. (2008) Abstract
Mori, S; Nakano, H; Aritomi, K; Wang, CR; Gunn, MD; Kakiuchi, T. Mice lacking expression of the chemokines CCL21-ser and CCL19 (plt mice) demonstrate delayed but enhanced T cell immune responses. Journal of Experimental Medicine. 2001;193:207-218. (2001) Abstract
Nakano, H; Yanagita, M; Gunn, MD. CD11c(+)B220(+)Gr-1(+) cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells. Journal of Experimental Medicine. 2001;194:1171-1178. (2001) Abstract
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. Journal of Experimental Medicine. 1999;189:451-460. (1999) Abstract
Gunn, MD; Ngo, VN; Ansel, KM; Ekland, EH; Cyster, JG; Williams, LT. A B-cell-homing chemokine made in lymphoid follicles activates Burkitt's lymphoma receptor-1. Nature. 1998;391:799-803. (1998) Abstract
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. Proceedings of the National Academy of Sciences of USA. 1998;95:258-263. (1998) Abstract