Quantitative in situ analysis of IL-6 mRNA and its producing cells in transplant kidneys

• Applicant: Dr. Henrik Junger
• Subject Area: General and Visceral Surgery
• Term: from 2017 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 381466120

After kidney transplant, major reasons for allograft dysfunction are rejection, interstitial fibrosis, tubular atrophy and infections. Significant proportions of the pathologic changes in the transplanted kidneys are linked to cellular and/or antibody-mediated anti-graft immunologic activity. Interleukin-6 is a key regulatory cytokine for both antibody- and T cell-mediated immune responses. Interleukin-6 has become a target molecule for new therapeutic strategies (Tocilizumab). The goal of this project is to better understand the mechanistic aspects of the complex interplay between local Interleukin-6 production and the inflammatory milieu in various forms of alloimmune injury in transplant kidneys. Further we want to assess the influence of Interleukin-6 blockade on the residual inflammatory milieu in a clinical Tocilizumab trial. This project propose to apply (i) novel second generation fluorescent in situ hybridization technology along with multiplexing immunofluorescence microscopy that allows simultaneous detection and quantification of several mRNAs and proteins in a single histological section. To use multiplexing immunofluorescence microscopy technology in combination with (ii) whole slide high resolution digital imaging and image analysis to quantitatively identify the precise cellular source of IL-6 mRNA signal in the transplanted kidney. The correlation between local Interleukin-6 production and the quantitative and qualitative aspects of the alloimmune inflammatory reaction, as aimed in this proposal, (a) may contribute to better understanding of the complex nature of cell-mediated anti-graft activity (b) may provide better morphologic tools to set apart alloimmune from reactive inflammation, and (c) may identify phenotypical patterns of injury to guide therapy and predict therapeutic responses.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Qizhi Tang, Ph.D.