Microsurgical models of murine organ transplantation have played a critical role in advancing our understanding of immunological pathways that regulate graft rejection and tolerance. Such models are important tools to develop therapies for transplant patients. As substantial differences exist between immune responses to various grafts, insights gained in one organ cannot be translated to other organs. Our laboratories have developed clinically relevant models of lung transplantation and re-transplantation in the mouse as well as novel approaches to image immune cell interactions in the murine pulmonary graft in real time. We and others have used these approaches to investigate clinically relevant lung-specific alloimmune responses. A dedicated microsurgery core was established at the initiation of this program project in 2015. The microsurgery core has proven instrumental in facilitating the execution of the experiments.
In aim 1 we will continue to standardize the quality of microsurgical and imaging procedures for all three projects in the proposal.
In aim 2 we will continue to standardize assessment of graft function and tissue harvest for all three projects.
In aim 3 we will maintain a system that provides unfettered access to microsurgical transplants and coordinates intravital imaging procedures for Projects 1 and 3.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
2P01AI116501-06
Application #
10024443
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2015-05-12
Project End
2025-05-31
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Ibrahim, Mohsen; Scozzi, Davide; Toth, Kelsey A et al. (2018) Naive CD4+ T Cells Carrying a TLR2 Agonist Overcome TGF-?-Mediated Tumor Immune Evasion. J Immunol 200:847-856
Takahashi, T; Hsiao, H M; Tanaka, S et al. (2018) PD-1 expression on CD8+ T cells regulates their differentiation within lung allografts and is critical for tolerance induction. Am J Transplant 18:216-225
Scozzi, Davide; Wang, Xingan; Liao, Fuyi et al. (2018) Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance. Am J Transplant :
Li, Wenjun; Luehmann, Hannah P; Hsiao, Hsi-Min et al. (2018) Visualization of Monocytic Cells in Regressing Atherosclerotic Plaques by Intravital 2-Photon and Positron Emission Tomography-Based Imaging-Brief Report. Arterioscler Thromb Vasc Biol 38:1030-1036
Hsiao, Hsi-Min; Fernandez, Ramiro; Tanaka, Satona et al. (2018) Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1?. J Clin Invest 128:2833-2847
Shi, Lei; Li, Kang; Guo, Yizhan et al. (2018) Modulation of NKG2D, NKp46, and Ly49C/I facilitates natural killer cell-mediated control of lung cancer. Proc Natl Acad Sci U S A 115:11808-11813
Hsiao, Hsi-Min; Scozzi, Davide; Gauthier, Jason M et al. (2017) Mechanisms of graft rejection after lung transplantation. Curr Opin Organ Transplant 22:29-35
Gelman, Andrew E; Fisher, Andrew J; Huang, Howard J et al. (2017) Report of the ISHLT Working Group on Primary Lung Graft Dysfunction Part III: Mechanisms: A 2016 Consensus Group Statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 36:1114-1120
Puyo, Carlos A; Peruzzi, Daniela; Earhart, Alexander et al. (2017) Endotracheal tube-induced sore throat pain and inflammation is coupled to the release of mitochondrial DNA. Mol Pain 13:1744806917731696
Gauthier, Jason M; Li, Wenjun; Hsiao, Hsi-Min et al. (2017) Mechanisms of Graft Rejection and Immune Regulation after Lung Transplant. Ann Am Thorac Soc 14:S216-S219

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