David Finlay

30 Nov 2024

New review article written by Cristhiane Favero de Aguiar and Carrie Corkish from my lab. They did a great job. www.nature.com/articles/s41... #SingleCell #Immunometabolism #ImmunoSky Approaches to investigate tissue-resident innate lymphocytes metabolism at the single-cell level

my.uplift.iePetition to #stopthegameI just signed the petition to #stopthegame - will you add your name too? No to a change of venue. No to forcing players to play a game they don't want to play. No to sportswashing. No to bending for g...

18 Sept

I just signed the petition to #stopthegame - will you add your name too? No to a change of venue. No to forcing players to play a game they don't want to play. No to sportswashing. No to bending for genocidal murderers. my.uplift.ie/petitions/pe... @uplift.ie

🧬 New in @eurjimmunol.bsky.social pDCs run a distinct iron programme: high TFRC, continuous iron flux, and targeted use in mitochondrial pathways, without increased iron storage. ➡️ However, lack of iron doesn’t limit IFN-I #paradox 🤯 🤷🏻‍♂️ #Immunology #Immunometabolism #pDC #TypeIIFN 🧵1/12

Together: ⚙️ High TFRC 🔄 Balanced iron flux 🎯 Targeted use in mitochondrial pathways → iron supports function without limiting it #InnateImmunity #Immunometabolism One idea, to be tested. Is constant endocytosis via TFRC a mode of antigen capture??? Is this a mad concept? 🧵11/12

More broadly: immune cells don’t just use nutrients - they organise specific flux programmes to support function. One idea, to be tested. Is constant endocytosis via TFRC a mode of antigen capture??? Is this a mad concept? Would love feedback 👇 #Immunology #SystemsImmunology 🧵end

We also detect ferroportin → iron export → pDCs maintain continuous iron flux (import + export), not storage → a distinct mode of iron handling An open question.....why?? 🧵9/12

Does iron availability regulate function? ❌ Iron chelation does NOT impair → IFN-I → TNF → pDC output is robust to iron perturbation 🧵10/12

But surprisingly: ❌ no increase in total cellular iron ❌ no increase in ferritin storage → pDCs are not accumulating iron 🧵7/12

What they do use iron for: 🔹 mitochondrial Fe-S proteins 🔹 heme-containing proteins → targeted allocation to functional systems #Mitochondria #IronMetabolism The mass of the mitochondrial proteome is significantly greater in pDC versus cDC1 and cDC2 🧵8/12

One signal stood out: 🔺 Transferrin receptor (TFRC) was extremely high in pDCs → much higher than other dendritic cells. Interestingly, they keep all their TFRC on the cell surface, which is not the case for cDC!! pointing to a major role for iron 🧵5/12

Functionally: ✅ pDCs show strong transferrin-mediated iron uptake ✅ higher than other splenic immune cells → consistent with high iron demand 🧵6/12

We profiled murine splenic pDCs and compared to cDC1, cDC2 and human pDC → revealing a highly conserved proteomic architecture across species #DendriticCells #Proteomics 🧵3/12

Most pathways were conserved, but key differences emerged in: 🔹 nutrient transport 🔹 amino acid use 🔹 central carbon metabolism → suggesting specialised metabolic wiring in pDCs 🧵4/12

🧵 pDCs are specialised antiviral cells that produce large amounts of type I IFN But how are they metabolically wired to support this? We used deep, quantitative proteomics directly ex vivo to map this 🧵2/12

pmc.ncbi.nlm.nih.govSingle Cell Glucose Uptake Assays: A Cautionary TaleAssays 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 ...

30 Jan

****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...

dx.plos.orgHexokinase 2 is an RNA-binding protein that regulates mRNA translation independently of glycolysis and induces melanoma cell proliferationHexokinase 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...

9 Nov 2025

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...

6 Nov 2025

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...

10 Oct 2025

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.

nature.comPeroxisomal metabolism of branched fatty acids regulates energy homeostasis - NatureA 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...

10 Oct 2025

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.

David Finlay reposted

Christian Frezza

@frezzalab.bsky.social

17 Sept 2025

Peroxisomal metabolism of branched fatty acids regulates energy homeostasis www.nature.com/articles/s41...

5 Oct 2025

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

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

5 Oct 2025

Sok SPM,…, Zhao M. P-glycoprotein expression skews mitochondrial dye measurements in T cells. Front Immunol. 2025 Jun www.frontiersin.org/journals/imm...

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

5 Oct 2025

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

cmghjournal.orgExercise-induced Metabolite N-lactoyl-phenylalanine Ameliorates Colitis by Inhibiting M1 Macrophage Polarization via the Suppression of the NF-κB Signaling PathwayAlthough 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...

4 Oct 2025

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

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

28 Sept 2025

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...

cell.comENPP1 governs the metabolic regulation of effector T cells in autoimmunity by detecting cytosolic mitochondrial DNAJi 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 ...

27 Sept 2025

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...

nature.comIron deficiency causes aspartate-sensitive dysfunction in CD8+ T cells - Nature CommunicationsIron 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.

27 Sept 2025

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...

pmc.ncbi.nlm.nih.govTrained immunity causes myeloid cell hypercoagulabilityThe 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...

27 Sept 2025

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...

David Finlay reposted

Philip O'Connor

@philipoconnor.bsky.social

16 Sept 2025

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...

ohchr.orgIsrael has committed genocide in the Gaza Strip, UN Commission findsGENEVA – 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...

David Finlay reposted

Ireland-Palestine Solidarity Campaign

@ipsc.bsky.social

17 Sept 2025

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...

trocaire.orgAct now for Palestine - rescue the Occupied Territories Bill - Trócaire

alz-journals.onlinelibrary.wiley.comData‐driven discovery of associations between prescribed drugs and dementia risk: A systematic reviewAbstract 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...

22 July 2025

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

David Finlay reposted

Eric Topol

@erictopol.bsky.social

21 Jan 2025

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/...

David Finlay reposted

Adrian Liston

@labliston.bsky.social

14 Jan 2025

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...

wellcomeopenresearch.orgwellcomeopenresearch.org

nature.comTriacylglycerol mobilization underpins mitochondrial stress recovery - Nature Cell BiologyBaker 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...

science.orgBile acid synthesis impedes tumor-specific T cell responses during liver cancerThe 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/...

faseb.onlinelibrary.wiley.comTime‐of‐day control of mitochondria regulates NLRP3 inflammasome activation in macrophagesThe 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/...

cell.comMetabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosineTEPP-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...

David Finlay reposted

Karen Slattery

@karen--s.bsky.social

13 Jan 2025

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

journals.lww.comLa dolce vita: fueling chimeric antigen receptor (CAR) T... : Immunometabolismy 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...

13 Jan 2025

La dolce vita: fueling chimeric antigen receptor (CAR) T... : Immunometabolism #immunometabolism #immunosky #glucose #CAR-T journals.lww.com/immunometabo...

cell.comInflammation switches the chemoattractant requirements for naive lymphocyte entry into lymph nodesLymph 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.

6 Jan 2025

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...

David Finlay reposted

RyanLab_TCD

@ryanlab.bsky.social

6 Jan 2025

📢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...

biorxiv.orgAn inherited mtDNA mutation remodels inflammatory cytokine responses in macrophages and in vivoImpaired 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...

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....

embopress.orgGlutamine sensing licenses cholesterol synthesis | The EMBO JournalimageimageWhether 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?

rupress.orgLactylation stabilizes TFEB to elevate autophagy and lysosomal activity | Journal of Cell Biology | Rockefeller University PressPosttranslational modifications play a crucial role in regulating autophagy and lysosome–related transcription factor TFEB. Huang et al. find the increase

Another important example of lactylation controlling metabolic pathways; stabilisation of TFEB to increase lysosomal activity. Will be interesting to see if this mechanism plays a role in #immunometabolism #immunology responses. rupress.org/jcb/article/...

doi.orgMetformin targets mitochondrial complex I to lower blood glucose levelsAcute oral metformin administration lowers blood glucose levels by targeting mitochondrial complex I.

Authors use an elegant transgenic model to demonstrate that acute oral administration of metformin targets mitochondrial complex I to lower blood glucose. A crucial contribution to the debate about the mechanisms of action of #metformin. #metabolism #glucose doi.org/10.1126/scia...

cell.comPyrimidine synthesis enzyme CTP synthetase 1 suppresses antiviral interferon induction by deamidating IRF3The intersection between cellular metabolism and innate immunity lacks understanding. Here, Rao and Qin et al. report that the metabolic enzyme, CTP synthetase 1, deamidates IRF3 to limit interferon induction, independent of its role in pyrimidine synthesis. This reveals how a key metabolic enzyme directly regulates innate immune activation.

#Immunometabolism role for Pyrimidine synthesis enzyme CTP synthetase-1. CTPS1 deaminates IRF3 and suppresses IFN response; important implications for antiviral #immunology? Yes indeed…. authors show that loss of CTPS1 elevates antiviral immune response in www.cell.com/immunity/ful...

David Finlay reposted

Anupam Patgiri

@apatgiri.bsky.social

4 Jan 2025

AMPK-regulated glycerol excretion maintains metabolic crosstalk between reductive and energetic stress www.nature.com/articles/s41...

nature.comAMPK-regulated glycerol excretion maintains metabolic crosstalk between reductive and energetic stress - Nature Cell BiologyZhai, Yang et al. report a central role for AMPK in regulating aldolase B-mediated glycerol synthesis and excretion under hypoxia as a mechanism to balance the trade-off between reductive and energy s...