ArticleProceedings of the National Academy of Sciences of the United States of America2026
TRIM21enhances IL-17A signaling and drives autoimmune myocarditis by promoting TRAF3 lysosomaldegradation in cardiac fibroblasts.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myocarditis is a potentially fatal disease that can progress to inflammatory dilated cardiomyopathy (DCMi), a condition that is a leading cause of noncongenital heart failure in young adults. However, the mechanisms driving the transition from acute myocarditis to DCMi remain poorly understood. Although IL-17A-mediated inflammation is a well-known driver of this progression, the intracellular regulators that sustain and amplify this response remain unclear. Here, we identify the E3 ubiquitin ligase TRIM21, which is upregulated in the hearts of DCMi patients and experimental autoimmune myocarditis (EAM) mice, as a key amplifier of IL-17A-driven inflammation in cardiac fibroblasts (CFs), promoting disease progression and fibrosis. TRIM21 deficiency significantly attenuates EAM progression, reducing inflammatory cell infiltration and fibrotic remodeling. Mechanistically, TRIM21 is induced by IL-17A in CFs and promotes K27-linked polyubiquitination and lysosomal degradation of TRAF3, a negative regulator of IL-17A signaling, thereby establishing a self-reinforcing IL-17A-TRIM21-TRAF3 positive feedback loop. Finally, specific knockdown of TRIM21 in CFs via the AAV9-Postn strategy effectively alleviates EAM severity. These findings identify TRIM21 as an intracellular mediator of sustained IL-17A signaling in myocarditis and highlight its potential as a therapeutic target for preventing progression to DCMi.
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.