David Finlay

Single Cell Glucose Uptake Assays: A Cautionary Tale Assays to monitor the metabolic state or nutrient uptake capacity of immune cells at a single cell level are increasingly in demand. One assay, used by many immunologists, employs 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose ...

****2-NBDG does not measure glucose uptake****

Just your regular reminder of this fact 😁.

See the rigorous proof of this fact in @lindavsinclair.bsky.social 2020 paper.

This paper was 6 years ago!! Stop using 2NBDG to measure glucose uptake already 🙄

pmc.ncbi.nlm.nih.gov/articles/PMC...

How immune cells partition intracellular nutrients and metabolic processes is so important, yet we know little about this.

New preprint from Beth Kelly 🇮🇪 in Erika Pearce’s lab studies the partitioning of cysteine in T cells and the consequences of metabolic perturbations for tumour responses.

Hexokinase 2 is an RNA-binding protein that regulates mRNA translation independently of glycolysis and induces melanoma cell proliferation Hexokinase 2 (HK2) is traditionally known for its metabolic role in glycolysis. This study shows that it also functions as an RNA-binding protein that regulates mRNA translation, particularly of SOX10...

Hexokinase 2, the latest glycolytic enzyme that also controls mRNA translation!

Nonmetabolic function of HK2 acting as an RBP and translation regulator.

dx.plos.org/10.1371/jour...

Preserving intracellular glutamate supports CD8 T cell anti tumour function.

Research from the Rathmell lab point to Glutamine synthetase a potential target for cancer immunotherapy

academic.oup.com/jimmunol/art...

3️⃣ Protect Irish citizens detained on the Gaza flotilla.
4️⃣ Suspend bilateral cooperation with Israel until international law is upheld.

The people of Ireland have spoken — we will not accept silence or complicity.

📧 Email: taoiseach@taoiseach.gov.ie and tanaiste@dfa.gov.ie to make your voice heard.

Ireland must act now.
Our government has failed to defend international law, failed to protect Irish citizens detained in international waters, and failed to enact the Occupied Territories Bill.

We demand action:
1️⃣ Implement the ICJ’s findings.
2️⃣ Enact the Occupied Territories Bill.

Peroxisomal metabolism of branched fatty acids regulates energy homeostasis - Nature A UCP1-independent mechanism of thermogenesis involving ATP-consuming metabolism of monomethyl branched-chain fatty acids in peroxisomes is described and a previously unrecognized role for peroxisomes...

Peroxisomal metabolism of branched fatty acids regulates energy homeostasis

www.nature.com/articles/s41...

Frontiers | P-glycoprotein expression skews mitochondrial dye measurements in T cells Assays to monitor metabolic parameters of immune cells at a single cell level provide efficient means to study immunometabolism. We show here that staining i...

Sok SPM,…, Zhao M. P-glycoprotein expression skews mitochondrial dye measurements in T cells. Front Immunol. 2025 Jun

www.frontiersin.org/journals/imm...

Caution : Expression of p-glycoprotein (ABCB1b) affects mitochondrial staining with MTG and TMRM

1-3k copies in NK cells.

Assess mitochondrial mass using multiple methods.
-10-nonyl acridine orange (NA0) stains mito-specific lipid cardiolipin,
-Antibody staining of proteins like ATP5b

Autophagy repression by antigen and cytokines shapes mitochondrial, migration and effector machinery in CD8 T cells Nature Immunology - Sinclair et al. combine quantitative proteomics and an autophagy flux reporter to map autophagy substrates and triggers during CD8 T cell differentiation. Proteins...

In case you missed it….great study from @lindavsinclair.bsky.social and Doreen Cantrell.

Autophagy and how it shapes CD8 T cell responses

-Differentially pruning naive and effector T cell proteomes
-Dynamically repressed by antigen receptors and inflammatory cytokines

rdcu.be/eJBFA

Exercise-induced Metabolite N-lactoyl-phenylalanine Ameliorates Colitis by Inhibiting M1 Macrophage Polarization via the Suppression of the NF-κB Signaling Pathway Although the anti-inflammatory benefits of exercise are well-documented, the specific mechanisms responsible for these advantages remain uncertain. N-lactoyl-phenylalanine (Lac-Phe), a major metabolit...

Exercise-induced Metabolite N-lactoyl-phenylalanine Ameliorates Colitis by Inhibiting M1 Macrophage Polarization. www.cmghjournal.org/article/S235...

Wonder how metformin induced LacPhe (pmc.ncbi.nlm.nih.gov/articles/PMC...) affects macrophages and gut inflammation. @immunometforum.bsky.social

Kupffer cell programming by maternal obesity triggers fatty liver disease - Nature In a mouse model, maternal obesity during pregnancy can lead to fatty liver disease in the offspring, driven by aberrant developmental programming of Kuppfer cells.

Maternal obesity alters function of offspring’s liver Kupffer cells leading to fatty liver disease.
Reprogramming during gestation requires #HIF1alpha.
Nice 👌. @masslab.bsky.social
I wonder how altered KC affects immunometabolism of other liver resident cells?
www.nature.com/articles/s41...

ENPP1 governs the metabolic regulation of effector T cells in autoimmunity by detecting cytosolic mitochondrial DNA Ji et al. demonstrate an abnormal differentiation of effector T cells in human SLE, identifying new functions of ENPP1 as an mtDNA sensor and transcription factor. ENPP1 sensing of mtDNA promotes the ...

ENPP1 senses cytosolic mtDNA and promotes increased Slc2a1 and glucose uptake. Ultimately contributes to mal-differentiation of T cells in SLE #mTorc1 #AMPK

Cell Reports www.cell.com/cell-reports...

Iron deficiency causes aspartate-sensitive dysfunction in CD8+ T cells - Nature Communications Iron has been shown to be necessary for the activation and differentiation of CD8+ T cells. Here the authors investigate changes in CD8+ T cell metabolism in iron limiting conditions and find that aspartate is increased yet downstream nucleotide synthesis is suppressed and addition of exogenous aspartate partially rescues T cell function.

Interesting insights into why iron is important for T cell proliferation, from @drakesmith-lab.bsky.social and Megan Teh (linkedin.com/in/megan-teh...) @ox.ac.uk

Iron scarcity creates a mitochondrial-located metabolic bottleneck in CD8 T cells.

www.nature.com/articles/s41...

Trained immunity causes myeloid cell hypercoagulability The pathogenic basis for increased thrombotic risk in individuals with inflammatory diseases is poorly understood. Myeloid cell “trained immunity” describes persistent innate immune cell memory arisin...

An interesting new angle on trained immunity and coagulation. Nice study by @aislingrehill.bsky.social and @rogerpreston.bsky.social from @rcsi.bsky.social

@researchireland.ie

pmc.ncbi.nlm.nih.gov/articles/PMC...

Israel has committed genocide in the Gaza Strip, UN Commission finds GENEVA – Israel has committed genocide against Palestinians in the Gaza Strip, the UN Independent International Commission of Inquiry on the Occupied Palestinian Territory, including East Jerusalem, a...

At an absolute minimum, Ireland must immediately pass the full Occupied Territories Bill (NOT the watered-down version) & end the transport of Israeli war matériel through Irish airspace.
And every Irish voter should be calling their TD tomorrow to ensure it happens.
www.ohchr.org/en/press-rel...

Act now for Palestine - rescue the Occupied Territories Bill - Trócaire

Please take this easy action, we must see sanctions on apartheid Israel for its genocide of Palestinians, we need, as a first step, the full Occupied Territories Bill enacted. #SanctionsNow
Act now for Palestine – rescue the Occupied Territories Bill
www.trocaire.org/petitions/ac...

10,000 people marched in Dublin this weekend. Ireland stands against genocide. Free Palestine.

Data‐driven discovery of associations between prescribed drugs and dementia risk: A systematic review Abstract Recent clinical trials on slowing dementia progression have led to renewed focus on finding safer, more effective treatments. One approach to identify plausible candidates is to assess whet...

A systematic review involving >130 million people and 1 million dementia cases found that anti-inflammatory medications, vaccinations, and antibiotics were associated with reduced dementia, whereas vitamins and supplements linked to higher risk
alz-journals.onlinelibrary.wiley.com/doi/10.1002/...

Our paper on nurturing a #PositiveResearchCulture within your #research #team published by @wellcometrust.bsky.social gives useful tips for your lab. As well as making you a good team leader, nurturing culture pays off in building your science: 1/11

wellcomeopenresearch.org/articles/9-3...

Triacylglycerol mobilization underpins mitochondrial stress recovery - Nature Cell Biology Baker et al. show that mitochondrial stress recovery requires mobilization of lipid droplet triacylglycerol stores to facilitate cardiolipin biosynthesis and mitochondrial biogenesis.

Lots of interest in how to maintain healthy mitochondria for effective cell therapy, like #NKcells for cancer immunotherapy. Some interesting clues in this article.
#immunosky #immunometabolism

Triacylglycerol mobilization underpins mitochondrial stress recovery
www.nature.com/articles/s41...

Bile acid synthesis impedes tumor-specific T cell responses during liver cancer The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that...

Exciting work from Sue Kaech’s lab @tcellogic.bsky.social

Tissue specific metabolites like #BileAcids in #Liver affect #CD8Tcell tumour responses

#immunometabolism #immunosky

Bile acid synthesis impedes tumor-specific T cell responses during liver cancer www.science.org/doi/10.1126/...

Time‐of‐day control of mitochondria regulates NLRP3 inflammasome activation in macrophages The circadian clock, orchestrated by BMAL1, regulates the expression of Nlrp3 and Il1b in response to lipopolysaccharide (LPS), causing time-of-day production of pro-IL-1β. Mitochondria exhibit time-....

More nice research from Annie Curtis’ lab on the circadian rhythm and the
#immunometabolism of macrophages.

#immunosky #mitochondria #inflammasome

Time‐of‐day control of mitochondria regulates NLRP3 inflammasome activation in macrophages faseb.onlinelibrary.wiley.com/doi/10.1096/...

Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine TEPP-46 activates PKM2 by inducing a tetramer formation, which leads to a metabolic reprogramming in macrophages, resulting in an increase in ATP and IL-10 production. Toller-Kawahisa et al. showed th...

PKM2 has always been intriguing; complex roles in some cells, here involving adenosine in #macrophages, simple glycolytic enzyme in #NKcells (doi.org/10.7554/eLif...)
#immunometabolism #immunosky
Metabolic reprogramming of macrophages by PKM2 promotes IL-10 via adenosine www.cell.com/cell-reports...

La dolce vita: fueling chimeric antigen receptor (CAR) T... : Immunometabolism y of patients relapse, which is concomitant with poor CAR T cell persistence. Similarly, the efficacy of CAR T cell therapy is limited in solid tumors, largely due to tumor antigen heterogeneity, immu...

Check out our new commentary on this interesting study by @justinaguerrero.bsky.social and team on Glut1 overexpressing CAR T cells. Excited to see what comes next for these metabolically enhanced T cells!
@davidfinlaytcd.bsky.social

La dolce vita: fueling chimeric antigen receptor (CAR) T... : Immunometabolism y of patients relapse, which is concomitant with poor CAR T cell persistence. Similarly, the efficacy of CAR T cell therapy is limited in solid tumors, largely due to tumor antigen heterogeneity, immu...

La dolce vita: fueling chimeric antigen receptor (CAR) T... : Immunometabolism
#immunometabolism #immunosky #glucose #CAR-T

journals.lww.com/immunometabo...

Inflammation switches the chemoattractant requirements for naive lymphocyte entry into lymph nodes Lymph node swelling is a well-known symptom of infection. A shift in the chemoattractant code controls lymphocyte recruitment from blood into inflamed lymph nodes, allowing lymphocytes to accumulate so that even rare antigen-specific cells can encounter their activating antigen.

Interesting new oxysterol research from Jason Cyster’s lab.

EBI2 (GPR183) and oxysterol ligand 7α,25-HC are required for lymphocyte homing to inflamed LNs.
#immunology #oxysterols
Inflammation switches the chemoattractant requirements for naive lymphocyte entry into LN www.cell.com/cell/fulltex...

An inherited mtDNA mutation remodels inflammatory cytokine responses in macrophages and in vivo Impaired mitochondrial bioenergetics in macrophages can drive hyperinflammatory cytokine responses, but whether this may also be caused by inherited mtDNA mutations is unknown. Here, we address this q...

📢Preprint alert! Very excited to share the first preprint from the lab spearheaded by stellar postdoc Eloïse Marques. An inherited mtDNA mutation remodels inflammatory cytokine responses in macrophages and in vivo. 1/n
www.biorxiv.org/content/10.1...

Metabolic #plasticity to Slc1a5 loss involving upregulation of macropinocytosis.

Important also for #immune cells to support glutamine requirements?
#immunometabolism

“Macropinocytosis mediates resistance to loss of glutamine transport in TNBC” www.embopress.org/doi/full/10....

Glutamine sensing licenses cholesterol synthesis | The EMBO Journal imageimageWhether cholesterol biosynthesis can be adjusted to the availability of input carbon sources remains unclear. This study demonstrates that glutamine is directly sensed by and required for ac...

“Glutamine sensing licenses cholesterol synthesis”

#glutamine interacts with SCAP to alter the ER to Golgi trafficking needed to activate #SREBP transcriptional response.

www.embopress.org/doi/full/10....

Is this relevant to #immunometabolism, such as SREBP-dependent #NKcell responses?