Chronic rejection represents the most important risk factor for poor long-term survival in clinicalheart and lung transplantation [1, 2]. In most cases, the ultimate cause of graft loss is a slowlydeveloping fibro-occlusive disease, whereby spaces within the organ fill up with collagen-forming cellsand fibrous material which in turn blocks passage of blood and air, ultimately destroying the functionalcapacity of the graft. When identifiable, infiltrates during chronic rejection are relatively enriched formonocytes/macrophages, and tend to lack Thi cytokines [e.g. IL-2 and IFN-y] that predominate in theeariy acute rejection phase [3]. Unfortunately, the immunosuppressive [IS] drugs currently in use fortransplant patients, mainly calcineurin inhibitors [CNI], corticosteroids and purine analogs, can reverseand prevent acute rejection but do little to halt the progress of fibro-obliteration. One possible reason forthe ineffectiveness of CNI drugs in chronic rejection is that CNI drugs target the calcineurin/NFATpathway that induces IFN-y and IL-2, inhibiting function of allospecific Th1 cells and 008

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI084853-04
Application #
8523763
Study Section
Special Emphasis Panel (ZAI1-QV-I)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$312,101
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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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