Date: Tuesday, May 5, 2015
Session Name: Poster Session D: Innate Immunity in Transplantation
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
In the context of kidney transplantation, NK cells may play an important role by targeting the allogeneic organ due to "missing-self recognition", which leads to allograft rejection. They can interact via NK ligands with renal epithelial cells. Immunosuppressants are supposed to block the innate and the adaptive immune system, but recent evidence suggests that they also may have an impact on non immune cells. Therefore, we investigated the effect of immunosuppressants on signaling, proliferation and chemokine production of kidney epithelial cells, chemokine levels were also studied in human kidney biopsies of transplanted patients.
Renal epithelial cells were incubated with calcineurin (CNI), mTOR inhibitors (mTORi) and Mycophenolic Acid for 48h. Surface expression of T/NK-cell ligands was analyzed by FACS, production of chemokines and phosphorylation of Akt/mTOR pathway components by multiplex technique. Renal epithelial cells were stimulated via plate bound antibodies against CD155, CD166 and interferons.
As expected, mTORi and partly CNI blocked phosphorylation of kinases within the PI3K/Akt pathway in renal cell lines. Chemokine secretion (e.g. CXCL8, CXCL12) was also suppressed by immunosuppressants while CD166, CD155 and HLA-class-I surface expression were slightly down regulated. In contrast, kidney cells triggered by CD166, CD155 or IFN secreted CXCL8, CXCL10 and other chemokines. Importantly, some of these chemokines were elevated in protein lysates of kidney biopsies from patients with biopsy proven rejection.
The impact of CNI and mTORi on epithelial cells may represent an underestimated mechanism with strong impact on tolerance/rejection after transplantation. We showed that renal epithelial cells can be activated via NK cell-ligands and they produce chemokines upon stimulation. According to our results, CXCL10 could be an important biomarker of rejection also in kidney biopsies which confirms published findings in urine.
To cite this abstract in AMA style:Akhdar A, Mueller B, Neudoerfl C, Lehner F, Stevanovic-Meyer M, Daemen K, Keil J, Haller H, Blume C, Falk C. The Influence of Immunosuppressive Drugs On the Epithelial Microenvironment in Solid Organ Transplantation – Identification of Biomarker Candidates for Rejection Vs. Tolerance [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/the-influence-of-immunosuppressive-drugs-on-the-epithelial-microenvironment-in-solid-organ-transplantation-identification-of-biomarker-candidates-for-rejection-vs-tolerance/. Accessed October 31, 2020.
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