David Sancho

Gracias @caixaresearch.bsky.social por el sólido apoyo a nuestra investigación.
Este reporte es sobre las cDC1s en la generación de respuesta adaptativa en #atherosclerosis & #immunotherapy en el hilo www.ahajournals.org/doi/10.1161/...

También apoyo fundamental en: www.nature.com/articles/s41...

This work identifies 'imidazole propionate' as a causal microbial metabolite that promotes atherosclerosis and shows that modulating its levels can potentially prevent cardiovascular disease risk, a promising therapeutic strategy.👇

Thanks, Maya! we need to develop: 1) testing of ImP in blood samples; 2) treatments for people with high ImP to inhibit its sensing (as in the paper) or its production (by inhibiting bacterial UrdA enzyme). Ideally, along with other treatments (e.g. potential synergy with lipid-lowering treatments).

Many thanks, Luis! 🫂 @lferreiramoita.bsky.social

A gut microbiota metabolite linked to atherosclerosis could revolutionise diagnosis and treatment A new study led by the Spanish National Centre for Cardiovascular Research (CNIC) and funded by the European Reasearch Council (ERC) has identified imidazole propionate (ImP), a metabolite produced by...

A gut microbiota metabolite linked to atherosclerosis could revolutionise diagnosis and treatment|ERC erc.europa.eu/news-events/...

Fantástico resumen por @manuelansede.bsky.social
🙏 @caixaresearch.bsky.social por financiar proyecto con 1 millón €
🙏 @ageinves.bsky.social por Severo Ochoa que inició el proyecto + 100K€ a nuestro lab
🙏 @erc.europa.eu ERC-CoG ERC-POC
#CNIC_CARDIO

Open acess: www.nature.com/articles/s41...

Revolución en la medicina: una molécula producida por bacterias del intestino causa la aterosclerosis, culpable de millones de muertes El descubrimiento, gracias a un experimento con cientos de trabajadores del Banco Santander en Madrid, abre la puerta a nuevos tratamientos más allá de reducir el colesterol

Revolución en la medicina: una molécula producida por bacterias del intestino causa la aterosclerosis, culpable de millones de muertes. El descubrimiento, del @sancholab.bsky.social, se acaba de publicar en la revista @nature.com 👇
elpais.com/salud-y-bien...

Thanks for the post, Ivan @lozanzi.bsky.social ! 🫂

Esta investigación del CNIC revela que un metabolito de la microbiota intestinal favorece la aterosclerosis.

Descubre más de la mano de uno de los investigadores del equipo 👇🧬

Gracias!!! 🤗🤗🤗

Thanks, Toño!!! 🫂

¡Gracias Carlos! 😊

Imidazole propionate is a driver and therapeutic target in atherosclerosis - Nature Imidazole propionate produced by gut microbiota is associated with atherosclerosis in mouse models and in humans, and causes the development of atherosclerosis through activation of the imidazoline-1 ...

🙏🏻Main funding by @caixaresearch.bsky.social (1M€).
Additional support by @ageinves.bsky.social @erc.europa.eu ERC-2016-Consolidator Grant 725091; ERC-2023-PoC;
Other funders: @comunidadmadrid.extwitter.link @contracancerinv.bsky.social @worldwidecancer.bsky.social
DOI nature.com/articles/s41...

📝 Study led by @annalaura-m.bsky.social & @iroblesv.bsky.social
🙏🏻collab #CNIC_CARDIO, #Borjaibanez1 starting this with me 7 years ago, Valentin Fuster, Fredrik Bäckhed on all ImP work, Göran Bergström IGT cohort, Kostas Stellos, Gabriel Nuñez Coral Barbas & many other col.

🧪 ImP is a circulating biomarker of early and active #atherosclerosis, with diagnostic and therapeutic potential.
📉 Its effects are lipid-independent: ImP–I1R–mTOR axis in myeloid cells as a new therapeutic target for atherosclerosis. Synergy with lipid-lowering therapy?
#immunosky #cardiosky

🧠 Mechanism: ImP acts through the imidazoline receptor I1R (Nischarin) in myeloid cells, activating mTOR and inducing TNF production.
🧬 Genetic or pharmacological blockade of I1R prevents #atherosclerosis development without lowering cholesterol.
#immunosky #cardiosky #microbiomesky

🐭 In mice, oral ImP administration is sufficient to drive #atherosclerosis, without altering cholesterol or glucose.
🧪 It triggers #innate and #adaptive #immune activation and systemic inflammation.
#immunosky #cardiosky #microbiomesky

In two independent human 🚶‍♀️🚶‍♂️cohorts (PESA @CNIC_CARDIO and IGT), plasma ImP levels were higher in people with subclinical #atherosclerosis, defined by multimodal advanced imaging (ultrasound, CT, PET-FDG). ImP linked to ACTIVE atherosclerosis in PESA.
#immunosky #cardiosky #microbiomesky

🔬 Using #untargeted #metabolomics in #atherosclerosis-prone mice, we identified ImP as strongly associated with plaque formation, even in the absence of cholesterol changes.
🦠 ImP concentration depend on gut #microbiota composition.
#immunosky #cardiosky #microbiomesky

Imidazole propionate is a driver and therapeutic target in atherosclerosis - Nature Imidazole propionate produced by gut microbiota is associated with atherosclerosis in mouse models and in humans, and causes the development of atherosclerosis through activation of the imidazoline-1 ...

💥 A gut microbe metabolite that drives #atherosclerosis?
Yes—Imidazole propionate (ImP) triggers vascular inflammation without changing cholesterol.
🧪 We show the pathway—and how to block it.
nature.com/articles/s41... #OpenAccess at
@Nature
@CNIC_CARDIO
#CVD #immunosky #cardiosky #microbiomesky

Thank you to my co-author @iroblesv.bsky.social and
@sancholab.bsky.social for believing in this project and to all the researchers who contributed to this work!!

Thanks, Christian! many years of team effort! 🫂

Congrats @iannaconelab.bsky.social & team on a wonderful work @natimmunol.nature.com on the immune regulation in the liver: CD4+ T cells license Kupffer cells to rescue CD8+ T cells through IL12 & mainly IL27. Highly relevant for liver immunotherapy!!!
👏🏻👏🏻👏🏻👏🏻👏🏻
#immunosky
👇🏻👇🏻👇🏻

📝 Study led by Miguel Galán #CNIC_CARDIO
🙏🏻collaborators @cicbiomagune.bsky.social, @ciml.bsky.social, @washumedicine.bsky.social
🙏🏻#Fundación La Caixa @ageinves.bsky.social @comunidadmadrid.bsky.social @contracancerinv.bsky.social @worldwidecancer.bsky.social
#immunotherapy #immunosky #cardiosky

🧩Conclusions:
✔️ cDC1s promote atherosclerosis via STING-driven IL-12 boost of Th1 & CD8+ T cell immunity
✔️ Targeted immunosuppression of cDC1s reduces inflammation and plaques
🧠 Novel precision strategy to tackle atherosclerosis beyond lipid control
#CardioImmunology #immunosky #cardiosky

🧩 A step closer to immune-based therapies for CVD
Anti-CLEC9A-dexamethasone NPs:
⬇️ Th1 CD4+
⬇️ Cytotoxic CD8+
⏸️ No effect on Tregs or Th17
🦠 Preserve acute antiviral immunity (tested in influenza infection)
➡️ Specific immunomodulation of cDC1s without global immunosuppression!
#immunosky #cardiosky

A new therapeutic tool:
Nanoparticles (NPs) decorated with anti-CLEC9A (cDC1-specific) and loaded with dexamethasone.
🎯 Target cDC1s with high specificity
📉 Reduce lesion size
🧾 No changes in lipid profile
🛡️ No toxicity to liver or kidneys
#NanoImmunotherapy #immunosky #cardiosky

What activates cDC1s?
We found that STING signaling in cDC1s is required for their pro-atherogenic role.
STING-deficient cDC1s =
🧬 Fewer plaques
⬇️ CD4+ Th1 and CD8+ IFN-γ+ T cells
🧠 STING is a crucial upstream driver in cDC1-mediated inflammation
#immunosky #cardiosky

scRNA-seq of aortic CD3+ T cells shows:
⬇️ Th1 and CD8+ IFN-γ+ T cells in the absence of cDC1s
⬇️ IL-12 expression
🧬 ↓ T cell clonality in CD4+ Th1 and CD8+ cytotoxic subsets
💡 cDC1s fuel local and systemic pro-inflammatory T cell responses
#immunosky #cardiosky

Even without FLT3L, selective depletion of cDC1s reduces plaque formation upon HCD feeding in two models: Xcr1-DTA OR Irf8Δ32 BM graft in Ldlr⁻/⁻
Fewer CD3+ T cells in aorta
No changes in cholesterol-body weight
➡️ cDC1s promote atherogenesis independent of lipid metabolism
#immunosky #cardiosky