Kidney Tertiary Lymphoid Structures in Lupus Nephritis Develop into Large Interconnected Networks and Resemble Lymph Nodes in Gene Signature.

Autor:	Dorraji SE; RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Science, UiT Arctic University of Norway, Tromsø, Norway., Kanapathippillai P; RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Science, UiT Arctic University of Norway, Tromsø, Norway., Hovd AK; RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Science, UiT Arctic University of Norway, Tromsø, Norway., Stenersrød MR; RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Science, UiT Arctic University of Norway, Tromsø, Norway., Horvei KD; RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Science, UiT Arctic University of Norway, Tromsø, Norway., Ursvik A; RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Science, UiT Arctic University of Norway, Tromsø, Norway., Figenschau SL; RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Science, UiT Arctic University of Norway, Tromsø, Norway., Thiyagarajan D; RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Science, UiT Arctic University of Norway, Tromsø, Norway., Fenton CG; Genomic Support Center, Department of Clinical Biology, Faculty of Health Science, UiT Arctic University of Norway, Tromso, Norway., Pedersen HL; RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Science, UiT Arctic University of Norway, Tromsø, Norway., Fenton KA; RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Science, UiT Arctic University of Norway, Tromsø, Norway. Electronic address: kristin.fenton@uit.no.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2020 Nov; Vol. 190 (11), pp. 2203-2225. Date of Electronic Publication: 2020 Aug 17.
DOI:	10.1016/j.ajpath.2020.07.015
Abstrakt:	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. (Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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