ArticleProceedings of the National Academy of Sciences of the United States of America2000
Genetic reconstitution of systemic lupus erythematosus immunopathology with polycongenic murine strains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
192 citing papers in PubMed, 401 citations in OpenAlex.
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- Pbx1 as a regulator of T-cell fate in autoimmunity.Frontiers in immunology · 2026Review
- Glycolysis inhibition functionally reprograms T follicular helper cells and reverses lupus.Cell reports · 2025Article
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- Gut Expansion of a Human Lupus Pathobiont is Associated With Autoantibody Production and T Cell Dysregulation.ACR open rheumatology · 2025Article
- Dysregulated Intestinal Host-Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models.Microorganisms · 2025Review
- Know Your ABCs: Discovery, Differentiation, and Targeting of T-Bet+ B Cells.Immunological reviews · 2025Review
- Animal models of lupus nephritis: the past, present and a future outlook.Autoimmunity · 2024Review
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- Androgens contribute to sex bias of autoimmunity in mice by T cell-intrinsic regulation of Ptpn22 phosphatase expression.Nature communications · 2024Article
- Microbial influences on severity and sex bias of systemic autoimmunity.Immunological reviews · 2024Review
- NADPH oxidase exerts a B cell-intrinsic contribution to lupus risk by modulating endosomal TLR signals.The Journal of experimental medicine · 2024Article
- Lupus susceptibility geneScience advances · 2024Article
- Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation.Nature communications · 2024Article
- Dietary tryptophan and genetic susceptibility expand gut microbiota that promote systemic autoimmune activation.bioRxiv : the preprint server for biology · 2024Article
- A global view of T cell metabolism in systemic lupus erythematosus.Frontiers in immunology · 2024Review
- FasClinical immunology (Orlando, Fla.) · 2024Article
- p16Lupus science & medicine · 2023Article
132 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
We previously produced three congenic strains carrying lupus susceptibility genes (Sle1-Sle3) from the lupus-prone NZM2410 mouse on the C57BL/6 background and characterized their component phenotypes. Sle1 mediates the loss of tolerance to nuclear antigens; Sle2 lowers the activation threshold of B cells; and Sle3 mediates a dysregulation of CD4(+) T cells. We have now created a collection of bi- and tricongenic strains with these intervals and assessed the autoimmune phenotypes they elicit in various combinations. Our results indicate that Sle1 is key for the development of fatal lupus. The combination of Sle1 with Sle2, Sle3, or the BXSB-derived autoimmune accelerating gene yaa results in the development of systemic autoimmunity with variably penetrant severe glomerulonephritis culminating in kidney failure. In contrast, two locus combinations of Sle2, Sle3, and yaa failed to mediate fatal disease. These results indicate that the loss of tolerance to chromatin mediated by Sle1 is essential for disease pathogenesis and identify the pathway occupied by Sle1 as a strategic target for therapeutic intervention in systemic lupus erythematosus. The coexpression of Sle1, Sle2, and Sle3 as a B6-triple congenic results in severe systemic autoimmunity and fully penetrant, fatal glomerulonephritis. These results demonstrate the fulfillment of the genetic equivalent of Koch's postulate, where susceptibility loci in a lupus-prone strain have been identified by a genome scan, isolated and functionally characterized by congenic dissection, and finally shown to mediate full disease expression when recombined in a normal genome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.