The overall objective of this project is to define the role of renal microenvironment in alloimmune responses. The hypotheses to be tested are that the microenvironment of a kidney allograft will determine the intensity of the infiltrating population of T cells and that the metabolism of heparan sulfate and eicosanoids will contribute to that microenvironment. The number of T lymphocytes responding to an allogeneic kidney graft will be determined by morphometric analysis as well as a direct quantitation of allogeneic DNA. The intensity will be examined as a function of antigenic disparity using as allogeneic donors mice which have MHC class I or MHC class II or both classes of MHC antigens deleted via homologous recombination. The control of alloimmune responses will then be evaluated from the perspective of the metabolism of heparan sulfate and PGE2. The extent to which the metabolism of these substances in an allogeneic kidney graft determines the intensity and diversity of the cellular immune response will be tested. Toward the objective of manipulating the microenvironment, a method will be developed that will allow the transfer of recombinant DNA into an organ graft leading to alteration in the metabolism of heparan sulfate and thus potentially of eicosinoids. The effect of this manipulation on alloimmune response will be tested.

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Duke University
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Allen, Irving C; Lich, John D; Arthur, Janelle C et al. (2012) Characterization of NLRP12 during the development of allergic airway disease in mice. PLoS One 7:e30612
Allen, Irving C; Jania, Corey M; Wilson, Justin E et al. (2012) Analysis of NLRP3 in the development of allergic airway disease in mice. J Immunol 188:2884-93
DiLillo, David J; Griffiths, Robert; Seshan, Surya V et al. (2011) B lymphocytes differentially influence acute and chronic allograft rejection in mice. J Immunol 186:2643-54
Ting, Jenny P Y; Duncan, Joseph A; Lei, Yu (2010) How the noninflammasome NLRs function in the innate immune system. Science 327:286-90
Arthur, Janelle C; Lich, John D; Ye, Zhengmao et al. (2010) Cutting edge: NLRP12 controls dendritic and myeloid cell migration to affect contact hypersensitivity. J Immunol 185:4515-9
Facemire, Carie S; Griffiths, Robert; Audoly, Laurent P et al. (2010) The impact of microsomal prostaglandin e synthase 1 on blood pressure is determined by genetic background. Hypertension 55:531-8
Jania, Leigh A; Chandrasekharan, Subhashini; Backlund, Michael G et al. (2009) Microsomal prostaglandin E synthase-2 is not essential for in vivo prostaglandin E2 biosynthesis. Prostaglandins Other Lipid Mediat 88:73-81
Crowley, Steven D; Vasievich, Matthew P; Ruiz, Phillip et al. (2009) Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis. J Clin Invest 119:943-53
Crowley, Steven D; Frey, Campbell W; Gould, Samantha K et al. (2008) Stimulation of lymphocyte responses by angiotensin II promotes kidney injury in hypertension. Am J Physiol Renal Physiol 295:F515-24
O'Connor, Brian P; Eun, So-Young; Ye, Zhengmao et al. (2008) Semaphorin 6D regulates the late phase of CD4+ T cell primary immune responses. Proc Natl Acad Sci U S A 105:13015-20

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