In this competing renewal application Dr. Luster proposes to study the role of the chemokine IP-10 in T cell recruitment and disease.
The first aim i s to determine the structural domains on IP-10 that mediate its chemotactic effects on T cells, as well as its anti-proliferative effects on endothelial cells. Solving the crystal structure of IP-10 is part of this aim.
The second aim i s to determine the roles of IP-10 and CXCR3 in murine models of inflammation and infection. Both IP-10 and CXCR3 knockout mice will be used in these studies.
The third aim i s to correlate the expression of IP-10 with the infiltration of CXCR3+ T cells in tissues isolated from patients with several selected diseases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA069212-04
Application #
2757803
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Finerty, John F
Project Start
1996-03-01
Project End
2003-12-31
Budget Start
1999-03-05
Budget End
1999-12-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Murray, Henry W; Luster, Andrew D; Zheng, Hua et al. (2017) Gamma Interferon-Regulated Chemokines in Leishmania donovani Infection in the Liver. Infect Immun 85:
Lian, Jeffrey; Luster, Andrew D (2015) Chemokine-guided cell positioning in the lymph node orchestrates the generation of adaptive immune responses. Curr Opin Cell Biol 36:1-6
Mikucki, M E; Fisher, D T; Matsuzaki, J et al. (2015) Non-redundant requirement for CXCR3 signalling during tumoricidal T-cell trafficking across tumour vascular checkpoints. Nat Commun 6:7458
Chow, Melvyn T; Luster, Andrew D (2014) Chemokines in cancer. Cancer Immunol Res 2:1125-31
Rocha, Viviane Zorzanelli; Folco, Eduardo J; Ozdemir, Cafer et al. (2014) CXCR3 controls T-cell accumulation in fat inflammation. Arterioscler Thromb Vasc Biol 34:1374-81
Woodruff, Matthew C; Heesters, Balthasar A; Herndon, Caroline N et al. (2014) Trans-nodal migration of resident dendritic cells into medullary interfollicular regions initiates immunity to influenza vaccine. J Exp Med 211:1611-21
Griffith, Jason W; Luster, Andrew D (2013) Targeting cells in motion: migrating toward improved therapies. Eur J Immunol 43:1430-5
Chen, Hui-Wen; King, Kevin; Tu, Jui et al. (2013) The roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus. J Immunol 191:4194-201
Ichikawa, Akihiko; Kuba, Keiji; Morita, Masayuki et al. (2013) CXCL10-CXCR3 enhances the development of neutrophil-mediated fulminant lung injury of viral and nonviral origin. Am J Respir Crit Care Med 187:65-77
Baptista, A P; Olivier, B J; Goverse, G et al. (2013) Colonic patch and colonic SILT development are independent and differentially regulated events. Mucosal Immunol 6:511-21

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