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. Importantly, substantial differences exist between immune responses to various grafts. Since the initial description of the orthotopic mouse lung transplant model by our laboratory we and others have relied on this technique to investigate lung-specific alloimmune responses. The overall goal is to establish a dedicated microsurgery core to facilitate the execution of experiments described in this program project.
In aim 1 we will establish a system to provide unfettered access to microsurgical transplants for all three projects in this proposal. We plan to accomplish this by coordinating access and timing of surgical procedures.
In aim 2 we will focus on standardizing the quality of microsurgical procedures for all three projects. We will accomplish this through systematic standardization of microsurgical procedure between all surgeons.
In aim 3 we plan to standardize techniques of intravital two- photon microscopy, a novel technique utilized by all three projects.
In aim 4 we plan to standardize assessment of graft function and tissue harvest.

Public Health Relevance

Mouse models of organ transplantation offer a reliable and reproducible method to study immune factors affecting graft survival. Immune responses differ between various transplantable organs. We plan to establish a microsurgery core facility to study immune responses specific to transplanted lungs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI116501-02
Application #
9066576
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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
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
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
Onyema, Oscar Okwudiri; Guo, Yizhan; Wang, Qing et al. (2017) Eosinophils promote inducible NOS-mediated lung allograft acceptance. JCI Insight 2:
Scozzi, Davide; Ibrahim, Mohsen; Menna, Cecilia et al. (2017) The Role of Neutrophils in Transplanted Organs. Am J Transplant 17:328-335

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