ArticleAmerican journal of physiology. Renal physiology2009
TGF-beta upregulation drives tertiary lymphoid organ formation and kidney dysfunction in calcineurin A-alpha heterozygous mice.
Article in American journal of physiology. Renal physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- HIF-1αImmunity · 2026Article
- Granzyme A-producing type 1 innate lymphoid cells promote salivary secretion in the aged submandibular gland.Inflammation and regeneration · 2026Article
- High Phosphate Load Induces De Novo Formation of Tertiary Lymphoid Structures in the Kidney.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Tertiary lymphoid structures in diseases: immune mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2024Review
- Lysyl oxidase inhibitors attenuate cyclosporin A-induced nephropathy in mouse.Scientific reports · 2021Article
- Kidney Tertiary Lymphoid Structures in Lupus Nephritis Develop into Large Interconnected Networks and Resemble Lymph Nodes in Gene Signature.The American journal of pathology · 2020Article
- Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Ectopic Tertiary Lymphoid Tissue in Inflammatory Bowel Disease: Protective or Provocateur?Frontiers in immunology · 2016Review
- Renal interstitial infiltration and tertiary lymphoid organ neogenesis in IgA nephropathy.Clinical journal of the American Society of Nephrology : CJASN · 2014Article
- Identification of novel genes associated with renal tertiary lymphoid organ formation in aging mice.PloS one · 2014Article
- Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin Aα null mice.PloS one · 2013Article
- Azathioprine as successful maintenance therapy in IgG4-related tubulointerstitial nephritis.Clinical kidney journal · 2012Article
- B cells in cardiac transplants: from clinical questions to experimental models.Seminars in immunology · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Calcineurin is an important intracellular signaling molecule which can be inhibited by cyclosporin resulting in immune suppression and nephrotoxicity. Previously, we reported that homozygous loss of the alpha isoform of calcineurin impairs kidney development and function and mimics many features of cyclosporin nephrotoxicity. However, early lethality of null mice prevented further study of renal changes. Alternatively, we examined aged heterozygous (CnAalpha(+/-)) mice. In addition to renal dysfunction and inflammation, we find that CnAalpha(+/-) mice spontaneously develop tertiary lymphoid aggregates in the kidney, small intestine, liver, and lung. Lymphoid aggregates contain both T cells and B cells and exhibited organization suggestive of tertiary lymphoid organs (TLOs). Kidney function and TLO formation were highly correlated suggesting that this process may contribute to nephrotoxicity. Consistent with previous findings, transforming growth factor (TGF)-beta is significantly increased in CnAalpha(+/-) mice. Neutralization of TGF-beta attenuated TLO formation and improved kidney function. In conclusion, we report that haploinsufficiency of CnAalpha causes uregulation of TGF-beta which contributes to chronic inflammation and formation of TLOs. While the process that leads to TLOs formation in transplant allografts is unknown, TLOs are associated with poor clinical prognosis. This study suggests that calcineurin inhibition itself may lead to TLO formation and that TGF-beta may be a novel therapeutic target.
Indexed as
Identifiers
What OpenQuestion holds
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.