David Sancho

Thanks, Samarth!

Always a mind-blowing talk from @sancholab.bsky.social
who showed, alongside cool data on macs, that cIII inhibition in cDC1 has functional consequence on anti-tumor immunity > mitochondrial ETC disruption impact on histone demethylase and alter PU.1 pioneer activity. Everything linked !

Thanks! 🫂

A type I interferon-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in macrophages Macrophage metabolism is intricately linked to cellular function. Contrasting with Toll-like receptor (TLR) stimulation, cytosolic nucleic acid sensin…

#WeekendRead! #InterferonPower! Dunphy @sancholab.bsky.social &co show @cp-immunity.bsky.social that in #macrophages, STING leads to type I #IFNs & ISG15-dependent ISGlatyion of mitochondrial proteins, increasing efferocytosis & driving epigenetic remodeling thus supporting inflammation resolution!

Thanks, Ivan! 🫂

#PhD in #immunometabolism on fatty acid oxidation in #macrophage function.
MSCA-DN: unimedizin-mainz.de/unlimited-ms...
For our DC8 position apply in parallel in 2 sites:
1. unimedizin-mainz.de/unlimited-ms...
2. cnic.es/en/convocato...
(DC8: NOT resident in Spain >12m in last 3 years)
#immunosky

The UNLIMITED consortium consists of the following partners: • University Medical Center of Mainz, Germany (Positions #3, #6, #15) • Carlos III National Cardiovascular Research Centre, Spain (Positions #8) • Technical University of Braunschweig, Germany (Positions #9) • Leiden University Medical Centre, Netherlands (Position #12) • Amsterdam Umc Foundation, Netherlands (Position #2) • University of Milan, Italy (Position #7) • University of Padua, Italy (Positions #4) • The Provost, Fellows, Foundation Scholars & The Other Members of Board, of The College of The Holy & Undivided Trinity, Ireland (Position #11) • National Centre for Scientific Research CNRS, France (Position #1) • University of Cologne, Germany (Position #13) • Luxembourg Institute of Health, Luxembourg (Position #14) • Medical University of Vienna, Austria (Position #10) • Vugene UAB, Lithuania (Position #5) Visit https://www.unimedizin-mainz.de/unlimited-msca/consortium.html for all the information and application. Applications must be done in parallel to local positions of each partner that you choose.

Available Positions and Research Topics The UNLIMITED network offers 15 Doctoral Candidate positions across four themes: (1) development of innovative tools for single-cell and spatial analysis of lipid immunometabolism (Subprojects 1–5); (2) molecular pathways linking lipid metabolism to immune activation and differentiation (Subprojects 6–10); (3) tissue-specific and systemic metabolic regulation of immune function (Subprojects 11–13); (4) discovery of therapeutic targets within lipid metabolism (Subprojects 14–15). Collectively, the UNLIMITED network will unravel the lipid–immune interface to generate mechanistic insights that guide the development of precision immunotherapy. Each researcher will receive interdisciplinary, intersectoral training across academia and industry, integrating advanced technologies with transferable and entrepreneurial skills.

Great opportunity for a #PhD on how lipid #metabolism regulates immune cell function in diseases such as cancer and autoimmunity. Train in immunology, bioIT, & metabolism.

Apply in parallel in:
1. UNLIMITED: www.unimedizin-mainz.de/unlimited-ms...
2. Local partner site that you choose.
#immunosky

Led by @gilliandunphy.bsky.social
Thx to coauthors
Thx #CNIC @ageinves.bsky.social @erc.europa.eu @comunidadmadrid.bsky.social @contracancerinv.bsky.social @worldwidecancer.bsky.social @caixaresearch.bsky.social criscancer.org
Open-access: www.cell.com/immunity/ful... #Immunosky

The take home mechanism: An IFN I→ISG15→ATP↑ & MMP↓ pathway enhances efferocytosis, while OMA1 driven fission & reduced ER–mito Ca²⁺ signaling lead to impaired H3K9 histone acetylation that limits ISG amplification—a built in resolve without overreacting program in macrophages. #immunosky

Physiological balance in infection. In a #vaccinia model, ISG15 or OMA1 deficiency leads to lower viral titers by day 7 (more ISGs), but also shows impaired #apoptotic cell clearance (more tissue damage), illustrating the trade off the axis manages during #resolution. #immunosky

Organellar dialog as a brake. IFN-I driven fission reduces ER–mitochondria contact sites, lowers mitochondrial Ca²⁺, and limits histone H3K9 acetylation → restrains ISG amplification. Pharmacologic blockade of mt Ca²⁺ (Ru360) or TCA entry (UK5099) prevents ISG over induction. #immunosky

Additionally, lower MMP activates OMA1, causing mitochondrial fission (confocal & TEM). Blocking fission (OMA1 KO or Mdivi 1) increases ISG induction, revealing #mitochondrial #fission as a negative regulator of ISGs. #immunosky

Function: #efferocytosis gets a boost. IFN-I increases #apoptotic cell uptake by macrophages. This requires #ISG15; #OMA1 mitochondrial protease is dispensable for this step. ISG15 deficiency shows impaired clearance of #apoptotic cells in vivo in thymic or peritoneal challenges. #Immunosky

#ISG15 is the switch. #IFNAR signaling ISGylates mitochondrial proteins (incl. ATP synthase subunit β) to raise ATP and lower MMP. ISGylation deficient ISG15 (AA) fails to rescue; wild type ISG15 (GG) restores ATP↑ & MMP↓
#immunosky

A distinct metabolic signature of #nucleic acid sensing: Unlike TLR ligands, #cytosolic nucleic acid sensing (#STING/#MAVS) or direct IFN I decreases mitochondrial membrane potential (MMP) without collapsing #OXPHOS. Measured by TMRM/JC 1; OCR remains intact. #immunosky

Excessive #inflammation?
We uncover @cp-immunity.bsky.social that #IFN-I via #ISG15 in macrophages lowers #mitochondrial membrane potential, boosts #efferocytosis, and self limits #ISG amplification: a built in brake that promotes resolution. Open-access: www.cell.com/immunity/ful...
#immunosky

A type I IFN-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in macrophages @cp-immunity.bsky.social @sancholab.bsky.social
www.cell.com/immunity/ful...

Don't miss the 2nd Conference of the European ImmunoMetabolism Network - EIMN2026
📅10-12th June 2026
📌Luxembourg

immunometnet.eu

@immunometeurope.bsky.social

linkedin.comevents/2ndconferenc...

7/ 🔬 What researcher @sancholab.bsky.social (CNIC) sees as an advance to improve cardiovascular health, artist and #laCaixaFoundFellows @guillermomora.bsky.social sees as a moving map. 🎨

They explain it to us in this #SnapshotsOfTheMonth. 👇

https://bit.ly/3XMZfOc

I had the pleasure of acting as an external PhD examiner for @aitorjarit.bsky.social in the lab of @sancholab.bsky.social 🇪🇸 during the summer.

Today I received his PhD thesis and a beautiful gift of a mitochondria illustrated in the style of an Andalusian tile.

Thank you very much!

Homeostatic control of energy metabolism by monocyte-derived macrophages | The EMBO Journal imageimageMacrophages play critical roles in the homeostatic control systems that maintain vital parameters within physiological ranges. This study characterizes how mouse monocyte-derived macrophages...

🧵 Thrilled to share our new work in @embojournal! Over a century after Metchnikoff recognized macrophages as central to organismal homeostasis, we reveal how they act as metabolic guardians through an unexpected mechanism.
www.embopress.org/doi/full/10....
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🌞 Day 2 begins at La Cristalera!

Today we welcome 2 Invited Plenary Speakers:
🔶 Prof. David Sancho, @sancholab.bsky.social (CNIC)
🔶 Prof. Susana Guerrero Salazar (University of Málaga)

✨Another full day of science, ideas, and inspiring talks ahead!
#RetreatIIBM_2025 #IIBmCSICUAM
@csic.es @uam.es

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 ! 🫂