Core C is central to the mission of the PPG since it will provide critical tools to PPG investigators for analyses of coinhibitory and costimulatory molecules to develop an understanding of the functions of positive and negative second signals in regulating T cell activation, tolerance and exhaustion. This Core will provide PPG investigators with an important and unique collection of mouse strains investigating the in vivo functions of T cell costimulatory/coinhibitory molecules individually, and their interplay. Core C has the expertise with both conventional and conditional transgenic and knockout technology that will enable the generation of novel mouse strains for analyzing the functions of immunoregulatory molecules in vivo.
Our specific aims are: 1) To generate novel knockout and transgenic mouse strains, conditionally or inducibly, 2) To generate mouse strains that facilitate analyses of the functions of coinhibitory/costimulatory molecules by breeding knockout mice with TCR transgenic or reporter mice, or analyses of interactions between coinhibitory receptors or interplay between positive and negative second signals by breeding various knockout mice with each other, 3) To maintain and provide mice of existing transgenic and knockout strains to PPG investigators. Core C will work closely with project investigators in all 3 projects, not only to provide them with transgenic and knockout strains, but also to generate novel strains based upon their findings in PPG projects. Core C also will provide knockout mice to Core B for immunization to generate novel mAbs. Taken together, these activities of Core C will provide PPG investigators with novel mouse strains for studying the roles of costimulatory and coinhibitory molecules in controlling T cell responses in mouse models of graft-versus-host disease, autoimmunity, and infection.
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|Zeiser, Robert; Sarantopoulos, Stefanie; Blazar, Bruce R (2018) B-cell targeting in chronic graft-versus-host disease. Blood 131:1399-1405|
|Blazar, Bruce R; MacDonald, Kelli P A; Hill, Geoffrey R (2018) Immune regulatory cell infusion for graft-versus-host disease prevention and therapy. Blood 131:2651-2660|
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|Sage, Peter T; Schildberg, Frank A; Sobel, Raymond A et al. (2018) Dendritic Cell PD-L1 Limits Autoimmunity and Follicular T Cell Differentiation and Function. J Immunol 200:2592-2602|
|Lu, Yunjie; Gao, Ji; Zhang, Shaopeng et al. (2018) miR-142-3p regulates autophagy by targeting ATG16L1 in thymic-derived regulatory T cell (tTreg). Cell Death Dis 9:290|
|Dixon, Karen O; Schorer, Michelle; Nevin, James et al. (2018) Functional Anti-TIGIT Antibodies Regulate Development of Autoimmunity and Antitumor Immunity. J Immunol 200:3000-3007|
|Fan, Martin Y; Turka, Laurence A (2018) Immunometabolism and PI(3)K Signaling As a Link between IL-2, Foxp3 Expression, and Suppressor Function in Regulatory T Cells. Front Immunol 9:69|
|Wu, Chuan; Chen, Zuojia; Xiao, Sheng et al. (2018) SGK1 Governs the Reciprocal Development of Th17 and Regulatory T Cells. Cell Rep 22:653-665|
|Juchem, Kathryn W; Sacirbegovic, Faruk; Zhang, Cuiling et al. (2018) PD-L1 Prevents the Development of Autoimmune Heart Disease in Graft-versus-Host Disease. J Immunol 200:834-846|
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