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
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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

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