- CORE C The Transgenic / Knockout Mouse Core provides a critical means by which the PPG will achieve its goals of understanding TIM-3 function and regulation of TIM-3 expression in cancer, autoimmune disease and chronic infections. This Core will provide PPG investigators with an important and unique collection of mouse strains for these studies. The Core has the expertise with both conventional and conditional transgenic and knockout technology that will enable the generation of novel mouse strains for analyzing TIM-3 function and the regulation of TIM-3 expression in vivo. To facilitate studies of TIM-3 function and TIM-3 expression, the Core also will generate TIM-3 conditional knockout strains by breeding TIM-3fl/fl mice with different Cre-driver strains. Initial priorities will be to breed TIM- 3fl/fl with dLck-cre and FoxP3-Cre. Core C also will breed carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM-1)-/- mice with TIM-3fl/fl x dLck-Cre mice. To enable studies of the cytokine regulation of TIM-3 expression, the Core will breed conditional transcription factor knockout mice with Cre strains of interest, cytokine reporter, and cytokine receptor knockout mice. In addition, Core C has access to FoxP3-GFP knock- in (KI) mice, which enable the visualization of the impact of transcription factors, cytokine/cytokine receptors on expression of TIM-3 on regulatory T cells in vivo. Finally, Core will serve as a repository for new mouse strains generated by the Core. The Transgenic/ Knockout Mouse Core will provide breeding pairs of these strains to PPG investigators as needed.

Public Health Relevance

- CORE C These studies will provide fundamental information about how, where, and when TIM-3 regulates tolerance, autoimmunity, and T cell exhaustion. The results of our studies will have implications for developing new therapies for human malignancies, chronic infection, and autoimmune diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI073748-09
Application #
9492816
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
9
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
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
Sabatos-Peyton, Catherine A; Nevin, James; Brock, Ansgar et al. (2018) Blockade of Tim-3 binding to phosphatidylserine and CEACAM1 is a shared feature of anti-Tim-3 antibodies that have functional efficacy. Oncoimmunology 7:e1385690
Meyer Zu Horste, Gerd; Przybylski, Dariusz; Schramm, Markus A et al. (2018) Fas Promotes T Helper 17 Cell Differentiation and Inhibits T Helper 1 Cell Development by Binding and Sequestering Transcription Factor STAT1. Immunity 48:556-569.e7
Iyer, Shankar S; Gensollen, Thomas; Gandhi, Amit et al. (2018) Dietary and Microbial Oxazoles Induce Intestinal Inflammation by Modulating Aryl Hydrocarbon Receptor Responses. Cell 173:1123-1134.e11
Chihara, Norio; Madi, Asaf; Kondo, Takaaki et al. (2018) Induction and transcriptional regulation of the co-inhibitory gene module in T cells. Nature 558:454-459
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
Dougall, William C; Kurtulus, Sema; Smyth, Mark J et al. (2017) TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy. Immunol Rev 276:112-120
Boggiano, Cesar; Eichelberg, Katrin; Ramachandra, Lakshmi et al. (2017) ""The Impact of Mycobacterium tuberculosis Immune Evasion on Protective Immunity: Implications for TB Vaccine Design"" - Meeting report. Vaccine 35:3433-3440
Carpenter, Stephen M; Yang, Jason D; Lee, Jinhee et al. (2017) Vaccine-elicited memory CD4+ T cell expansion is impaired in the lungs during tuberculosis. PLoS Pathog 13:e1006704
Wang, Chao; Singer, Meromit; Anderson, Ana C (2017) Molecular Dissection of CD8+ T-Cell Dysfunction. Trends Immunol 38:567-576

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