David Finlay
@davidfinlaytcd.bsky.social
Interested in all things Immunometabolism ORCID:0000-0003-2716-6679 Saoirse don Phailistín
🧬 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
****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...
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 ...
pmc.ncbi.nlm.nih.gov
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...
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...
dx.plos.org
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...
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 www.nature.com/articles/s41...
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...
nature.com
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
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
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...
rdcu.be
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
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...
cmghjournal.org
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...
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.
nature.com
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...
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 ...
cell.com
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...
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.
nature.com
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...
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...
pmc.ncbi.nlm.nih.gov
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...
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...
ohchr.org
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...
Act now for Palestine - rescue the Occupied Territories Bill - Trócaire
trocaire.org
10,000 people marched in Dublin this weekend. Ireland stands against genocide. Free Palestine.
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/...
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...
alz-journals.onlinelibrary.wiley.com
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.org
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...
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.
nature.com
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/...
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...
science.org
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/...
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-....
faseb.onlinelibrary.wiley.com
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...
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...
cell.com
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...
journals.lww.com
La dolce vita: fueling chimeric antigen receptor (CAR) T... : Immunometabolism #immunometabolism #immunosky #glucose #CAR-T journals.lww.com/immunometabo...
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...
journals.lww.com
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...
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.
cell.com
📢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...
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...
biorxiv.org
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” #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?
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...
embopress.org
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/...
Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity | Journal of Cell Biology | Rockefeller University Press
Posttranslational modifications play a crucial role in regulating autophagy and lysosome–related transcription factor TFEB. Huang et al. find the increase
rupress.org
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...
Metformin targets mitochondrial complex I to lower blood glucose levels
Acute oral metformin administration lowers blood glucose levels by targeting mitochondrial complex I.
doi.org