Despite improvements in management of acute allograft rejection and 1 year survival of allografts, many organs succumb sooner or later to chronic allograft rejection/injury. Important contributor to this process is chronic vascular rejection in any organ, and bronchilitis obliterans in transplanted lungs. In the present program project we propose that the abnormal deposits of extracellular matrix seen in bronchioles with obliterative bronchiolitis and arteries with chronic allograft vasculopathy obey to an abnormal humoral and cellular immunity to the generation of excess col(V) al homotrimers in the extracellular matrix. The goal of the Core C, "Pathology Core" is to provide the histopathology and immunopathology analysis in support of the three proposed projects of the program. Specifically, animal models and human tissues derived from the projects will be analyzed for histomorphologic changes, immunohistochemistry and specialized tissue analysis techniques to characterize extracellular matrix components, and cellular, humoral and soluble mediators of the immune response related to autoimmunity to collagen V in chronic allograft injury. The Core will ensure the appropriate flow of human and animal model tissue between the different institution and laboratories of the program as well as the adequate use of resources pertinent to the Core. The Core has proposed 5 main aims to aid the program projects at different steps, including diagnostic histopathology of biopsies, immunohistochemistry of animal models and human tissue, laser capture microdissection, morphometric analysis and detection of cytokines in human and animal samples. The Core leader. Dr. Jose R. Torrealba, a pathologist specialized in organ transplantation, will provide all the diagnostic histopathology and coordinate the activities of the Core. Numerous manuscripts, including recent publications with the program project Pis, demonstrate the collaboration capabilities and resources of the Core.

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The pathology Core will provide histopathology, immunohistochemistry and specialized tissue section analysis for the development and completion of each project of the program project. It will oversee the adequate handling and flow of biological material for tissue analysis between the different institutions and laboratories participating in the program as well as the rational use of resources pertinent to the Core.

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Pandya, Pankita H; Wilkes, David S (2014) Complement system in lung disease. Am J Respir Cell Mol Biol 51:467-73
Weber, Daniel J; Gracon, Adam S A; Ripsch, Matthew S et al. (2014) The HMGB1-RAGE axis mediates traumatic brain injury-induced pulmonary dysfunction in lung transplantation. Sci Transl Med 6:252ra124
Gracon, Adam S A; Wilkes, David S (2014) Lung transplantation: chronic allograft dysfunction and establishing immune tolerance. Hum Immunol 75:887-94
Shah, Rupal J; Emtiazjoo, Amir M; Diamond, Joshua M et al. (2014) Plasma complement levels are associated with primary graft dysfunction and mortality after lung transplantation. Am J Respir Crit Care Med 189:1564-7
Walline, Crystal C; Deffit, Sarah N; Wang, Nan et al. (2014) Virus-encoded ectopic CD74 enhances poxvirus vaccine efficacy. Immunology 141:531-9
Sullivan, J A; Jankowska-Gan, E; Shi, L et al. (2014) Differential requirement for P2X7R function in IL-17 dependent vs. IL-17 independent cellular immune responses. Am J Transplant 14:1512-22
Sullivan, Jeremy A; Adams, Andrew B; Burlingham, William J (2014) The emerging role of TH17 cells in organ transplantation. Transplantation 97:483-9
Emtiazjoo, Amir M; Wilkes, David S (2013) Humoral immunity and the development of obliterative bronchiolitis after lung transplantation: is there a link? Am J Respir Cell Mol Biol 48:145-9
Lockridge, Jennifer L; Zhou, Ying; Becker, Yusof A et al. (2013) Mice engrafted with human fetal thymic tissue and hematopoietic stem cells develop pathology resembling chronic graft-versus-host disease. Biol Blood Marrow Transplant 19:1310-22
Vittal, Ragini; Fan, Lin; Greenspan, Daniel S et al. (2013) IL-17 induces type V collagen overexpression and EMT via TGF-ýý-dependent pathways in obliterative bronchiolitis. Am J Physiol Lung Cell Mol Physiol 304:L401-14

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