Abstract

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

  Funding Agency

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

  Institution

Name
Indiana University-Purdue University at Indianapolis
Department
Type
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202

  Publications

Haynes, Lynn D; Julliard, Walker A; Mezrich, Joshua D et al. (2018) Specific Donor HLA-DR Types Correlate With Altered Susceptibility to Development of Chronic Lung Allograft Dysfunction. Transplantation 102:1132-1138
Sullivan, J A; Jankowska-Gan, E; Hegde, S et al. (2017) Th17 Responses to Collagen Type V, k?1-Tubulin, and Vimentin Are Present Early in Human Development and Persist Throughout Life. Am J Transplant 17:944-956
Park, Arick C; Phan, Noel; Massoudi, Dawiyat et al. (2017) Deficits in Col5a2 Expression Result in Novel Skin and Adipose Abnormalities and Predisposition to Aortic Aneurysms and Dissections. Am J Pathol 187:2300-2311
Muir, Alison M; Massoudi, Dawiyat; Nguyen, Ngon et al. (2016) BMP1-like proteinases are essential to the structure and wound healing of skin. Matrix Biol 56:114-131
Pandya, Pankita H; Fisher, Amanda J; Mickler, Elizabeth A et al. (2016) Hypoxia-Inducible Factor-1? Regulates CD55 in Airway Epithelium. Am J Respir Cell Mol Biol 55:889-898
Park, Arick C; Huang, Guorui; Jankowska-Gan, Ewa et al. (2016) Mucosal Administration of Collagen V Ameliorates the Atherosclerotic Plaque Burden by Inducing Interleukin 35-dependent Tolerance. J Biol Chem 291:3359-70
Agashe, Vrushali V; Burlingham, William J (2015) Autoimmune Reactivity in Graft Injury: Player or Bystander? Curr Transplant Rep 2:211-221
Wu, Qiang; Gupta, Pawan Kumar; Suzuki, Hidemi et al. (2015) CD4 T Cells but Not Th17 Cells Are Required for Mouse Lung Transplant Obliterative Bronchiolitis. Am J Transplant 15:1793-1804
Park, Arick C; Phillips, Charlotte L; Pfeiffer, Ferris M et al. (2015) Homozygosity and Heterozygosity for Null Col5a2 Alleles Produce Embryonic Lethality and a Novel Classic Ehlers-Danlos Syndrome-Related Phenotype. Am J Pathol 185:2000-11
Pandya, Pankita H; Wilkes, David S (2014) Complement system in lung disease. Am J Respir Cell Mol Biol 51:467-73

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