ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021
A cell-penetrating CD40-TRAF2,3 blocking peptide diminishes inflammation and neuronal loss after ischemia/reperfusion.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed, 15 citations in OpenAlex.
- Aqueous humour cytokine profiles in retinal vein occlusion: a comparative study of acute, chronic recurrent, and control eyes.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Advances in the Role of the CD40-CD154 Pathway in the Pathogenesis of Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- Identification and validation of oxidative stress signature genes in the trabecular meshwork of glaucoma.Scientific reports · 2025Article
- CD40 Induces Unfolded Protein Response, Upregulation of VEGF, and Vascular Leakage in Diabetic Retinopathy.Diabetes · 2025Article
- CD40 Upregulation in the Retina of Patients With Diabetic Retinopathy: Association With TRAF2/TRAF6 Upregulation and Inflammatory Molecule Expression.Investigative ophthalmology & visual science · 2023Article
- Autophagy in protists and their hosts: When, how and why?Autophagy reports · 2023Article
- Disruption of retinal inflammation and the development of diabetic retinopathy in mice by a CD40-derived peptide or mutation of CD40 in Müller cells.Diabetologia · 2022Article
- Single-cell RNA sequencing reveals a landscape and targeted treatment of ferroptosis in retinal ischemia/reperfusion injury.Journal of neuroinflammation · 2022Article
- Regulations of Retinal Inflammation: Focusing on Müller Glia.Frontiers in cell and developmental biology · 2022Review
- A cell-penetrating CD40-TRAF2,3 blocking peptide diminishes inflammation and neuronal loss after ischemia/reperfusion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Recent Advances in the Roles of Autophagy and Autophagy Proteins in Host Cells DuringFrontiers in cell and developmental biology · 2021Review
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 2 institutions in 1 country.
Funding
Abstract
While the administration of anti-CD154 mAbs in mice validated the CD40-CD154 pathway as a target against inflammatory disorders, this approach caused thromboembolism in humans (unrelated to CD40 inhibition) and is expected to predispose to opportunistic infections. There is a need for alternative approaches to inhibit CD40 that avoid these complications. CD40 signals through TRAF2,3 and TRAF6-binding sites. Given that CD40-TRAF6 is the pathway that stimulates responses key for cell-mediated immunity against opportunistic pathogens, we examined the effects of pharmacologic inhibition of CD40-TRAF2,3 signaling. We used a model of ischemia/reperfusion (I/R)-induced retinopathy, a CD40-driven inflammatory disorder. Intravitreal administration of a cell-penetrating CD40-TRAF2,3 blocking peptide impaired ICAM-1 upregulation in retinal endothelial cells and CXCL1 upregulation in endothelial and Müller cells. The peptide reduced leukocyte infiltration, upregulation of NOS2/COX-2/TNF-α/IL-1β, and ameliorated neuronal loss, effects that mimic those observed after I/R in Cd40-/- mice. While a cell-penetrating CD40-TRAF6 blocking peptide also diminished I/R-induced inflammation, this peptide (but not the CD40-TRAF2,3 blocking peptide) impaired control of the opportunistic pathogen Toxoplasma gondii in the retina. Thus, inhibition of the CD40-TRAF2,3 pathway is a novel and potent approach to reduce CD40-induced inflammation, while likely diminishing the risk of opportunistic infections that would otherwise accompany CD40 inhibition.
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.