Kidney Tertiary Lymphoid Structures in Lupus Nephritis Develop into Large Interconnected Networks and Resemble Lymph Nodes in Gene Signature
| Autor: | Hege Lynum Pedersen, Kristin A. Fenton, Seyed Esmaeil Dorraji, Aud-Malin Karlsson Hovd, anita Ursvik, Kjersti Daae Horvei, Christopher Graham Fenton, Mikael Ryan Stenersrød, Stine Figenschau, Premasany Kanapathippillai, Dhivya Thiyagarajan |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty High endothelial venules Lupus nephritis Biology Kidney Pathology and Forensic Medicine Mice 03 medical and health sciences 0302 clinical medicine medicine Animals VDP::Medisinske Fag: 700 Lymph node B cell Follicular dendritic cells Gene Expression Profiling Germinal center Kidney metabolism Dendritic Cells medicine.disease Lupus Nephritis VDP::Medical disciplines: 700 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Lymph Nodes Lymph 030215 immunology |
| Zdroj: | The American Journal of Pathology. 190:2203-2225 |
| ISSN: | 0002-9440 |
| Popis: | Immune aggregates organized as tertiary lymphoid structures (TLS) are observed within the kidneys of patients with systemic lupus erythematosus and lupus nephritis (LN). Renal TLS was characterized in lupus-prone New Zealand black × New Zealand white F1 mice analyzing cell composition and vessel formation. RNA sequencing was performed on transcriptomes isolated from lymph nodes, macrodissected TLS from kidneys, and total kidneys of mice at different disease stages by using a personal genome machine and RNA sequencing. Formation of TLS was found in anti–double-stranded DNA antibody–positive mice, and the structures were organized as interconnected large networks with distinct T/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 lymph nodes revealed a similar gene signature of TLS and lymph nodes. The up-regulated genes within the kidneys of lupus-prone mice during LN development reflected TLS formation, whereas the down-regulated genes were involved in metabolic processes of the kidney cells. A comparison with human LN gene expression revealed similar up-regulated genes as observed during the development of murine LN and TLS. In conclusion, kidney TLS have a similar cell composition, structure, and gene signature as lymph nodes and therefore may function as a kidney-specific type of lymph node. |
| Databáze: | OpenAIRE |
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