Kristin A. Fenton, Norway
UiT The arctic university of Norway RNA and molecular pathology research groupPresenter of 1 Presentation
KIDNEY TERTIARY LYMPHOID STRUCTURES IN LUPUS NEPHRITIS DEVELOP INTO LARGE INTERCONNECTED NETWORKS AND RESEMBLES LYMPH NODES IN GENE SIGNATURE.
Abstract
Background and Aims
Immune aggregates organized as tertiary lymphoid structures (TLS) are observed within kidneys of systemic lupus erythematosus (SLE) patients with lupus nephritis (LN). The gene profile of kidney specific TLS compared to the kidney and lymph node (LyN) during LN progression has not yet been studied.
Methods
We characterized renal TLS in lupus-prone (NZBxNZW) F1 mice with respect to cell composition and vessel formation. Ribonucleic acid (RNA) sequencing was performed on transcriptomes isolated from LyN, macro-dissected TLS from kidneys, and total kidneys of mice at different disease stages by using Ion Torrent Personal Genome Machine (Ion PGM) and RNAseq from Illumina.
Results
Formation of TLS was found in anti-dsDNA antibody positive mice and the structures were organized as interconnected large networks with distinct T and B cell zones with adjacent dendritic cells, macrophages, plasma cells, high endothelial venules, supporting follicular dendritic cells network, and functional germinal centers. Comparison of gene profiles of whole kidney, renal TLS and LyN revealed a similar gene signature of TLS and LyN. The upregulated genes within the kidneys of lupus-prone mice during the development of LN reflected the TLS formation, while the downregulated genes were involved in metabolic processes of the kidney cells. A comparison with human LN gene expression revealed similar upregulated genes as observed during the development of murine LN and TLS.
Conclusions
We conclude that kidney TLS have a similar cell composition, structure and gene signature as LyN, and therefore may function as a kidney specific type of LyN.