Back Signaling of HLA Class I Molecules and NK Cell Receptor Ligands in Renal Epithelial Cells Contributes to the Rejection-Specific Microenvironment
1Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany, 2Nephropathology Unit, Institute of Pathology, Hannover Medical School, Hannover, Germany, 3Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany, 4Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
Institute of Technical Chemistry, Leibniz University, Hannover, Germany, 5Institute of Transplant Immunology, Hannover Medical School
DZIF, German Center for Infection Research, TTU-IICH, Hannover/Braunschweig, Germany
Meeting: 2019 American Transplant Congress
Abstract number: A196
Keywords: HLA antibodies, Kidney, Natural killer cells, Rejection
Session Information
Session Name: Poster Session A: Kidney Chronic Antibody Mediated Rejection
Session Type: Poster Session
Date: Saturday, June 1, 2019
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: During the last years, diverse harming mechanisms of donor-specific antibodies (DSA) to endothelial cells have been studied accompanied by an emerging evidence of NK cell involvement in antibody-mediated rejection (ABMR). However, the role of kidney epithelial cells was less intensively examined and maybe underestimated despite their potential impact as targets for DSA and NK cells.
*Methods: Therefore, we investigated proximal tubular epithelial cells (PTEC) upon stimulation via HLA class I and NK cell receptor ligands, CD155 and CD166, which were selected based on their potential signal-transducing capacities.
*Results: Upon stimulation with anti-HLA and anti-CD166 mab, PTEC secreted IL-6, CXCL8, CXCL10, IL-12p40, IL-1RA, and sICAM-1 (all p<0.05). Clinically approved immunosuppressive drugs and other signal inhibitors were unable to block this back signaling and, hence, revealed a complex regulatory network upon triggering HLA class I and NK cell receptor ligands. This PTEC cytokine response was compared to the cytokine/chemokine microenvironment of 37 kidney transplant biopsies, classified as unsuspicious, T-cell-mediated rejection (TCMR), borderline or ABMR rejection according to the BANFF classification. Rejection, especially ABMR, was associated with a distinct cytokine milieu, guided by significantly higher levels of chemokines (CXCL9, CXCl10 and CCL5, all p<0.05).
*Conclusions: Based upon, we suggest, that via PTEC back signaling, chemokine release strengthens the ABMR-process by attraction of other immunocytes and this contributes to the destructing pathomechanisms within kidney allograft rejection.
To cite this abstract in AMA style:
Chichelnitskiy E, Egelkamp J, Daemen K, Keil J, Neudörfl C, Bräsen J, Schmitz J, Haller H, Blume C, Falk C. Back Signaling of HLA Class I Molecules and NK Cell Receptor Ligands in Renal Epithelial Cells Contributes to the Rejection-Specific Microenvironment [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/back-signaling-of-hla-class-i-molecules-and-nk-cell-receptor-ligands-in-renal-epithelial-cells-contributes-to-the-rejection-specific-microenvironment/. Accessed November 22, 2024.« Back to 2019 American Transplant Congress