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Identification of key genes involved in the formation of tertiary lymphoid organs in the central nervous system in a B-cell dependent mouse model of multiple sclerosis

Rohde, J;

In patients suffering from a specific form of MS, inflammatory infiltrates were detected in the meninges, which were similar in their structure to lymphoid tissue. The presence of these infiltrates was associated with a more severe disease progression. The mouse model of B-cell-dependent MP4-induced experimental autoimmune encephalomyelitis (EAE) shows infiltrates in the cerebellums of mice that are similar in structure and organization to infiltrates in humans. The aim of this work was first to isolate intact and stable ribonucleic acids (RNA) from mouse infiltrates. We then identified genes that were upregulated in the B-cell infiltrates during the cerebral inflammatory response. We compared the potential for RNA isolation in paraffin-embedded tissue and cryofixed tissue. We performed laser capture microdissection (LCM) followed by gene sequencing of cerebral B-cell infiltrates in mice. MOG:35-55-induced EAE was used as a B-cell-independent control model. Furthermore, we compared the results with the expression profiles of secondary lymphoid organs. RNA isolation from cryofixed tissue was superior to that from paraffin-embedded tissue. In this study, we observed 43 genes that were significantly upregulated during the development of B-cell infiltrates in the cerebellums of MP4-immunized mice. Of these genes, 14 have already been mentioned in the context of MS and some are the subject of active research. However, some of the remaining genes also show promising immunological properties. The exact role of the genes and possibly their influence on each other offer great scope for further research.