bims-nimamd Biomed News
on Neuroimmunity and neuroinflammation in ageing and metabolic disease
Issue of 2026–03–29
twenty papers selected by
Fawaz Alzaïd, Sorbonne Université
  1. Often forgotten but essential: long-chain acyl-CoAs in metabolic control.
  2. Associations of continuous glucose monitor derived time in range and glycaemic variability with diet lifestyle and demographics.
  3. Commensals join the effector game.
  4. Charting the human brain's lifelong functional organization.
  5. PLIN5 phosphorylation orchestrates mitochondria lipid-droplet coupling to control hepatic lipid flux and steatosis.
  6. A transcriptomic microglia taxonomy across mouse and human pathologies.
  7. How the war in Iran is reshaping the energy landscape.
  8. Beyond bystanders: How β cell stress shapes the autoimmune response in T1D.
  9. Atlas of one-carbon metabolism in conventional and germ-free mice reveals folate as a key determinant of biochemical pathways.
  10. Parasites trigger epithelial cell crosstalk to drive gut-brain signalling.
  11. In vivo metabolic tagging and targeting of circulating red blood cells.
  12. Revisiting the burden and patterns of myocardial infarction in type 1 diabetes.
  13. Cardiovascular PIEZO discovery continues apace to reveal myocardial nerves feeling posture and blood loss.
  14. Distinctive DNA sequence features define epigenetic longevity of inflammatory memory.
  15. Motherhood derails women's academic careers - these data reveal how and why.
  16. The many pathways driving liver inflammation in MASH.
  17. Palmitate-induced mitochondrial damage restricts histone acetylation in CD8 T cells to impair antitumor immunity.
  18. The expanding role of mitochondria-lipid droplet contacts in liver and their disruption by MASLD.
  19. Aging disrupts sympathetic innervation of the thymus.
  20. Mitochondrial lactate venting limits oxidative stress.
  1. Nat Metab. 2026 Mar 26.
    Often forgotten but essential: long-chain acyl-CoAs in metabolic control.
    Nils J Færgeman.
      
    DOI:  https://doi.org/10.1038/s42255-026-01509-9
  2. Nat Commun. 2026 Mar 27.
    Associations of continuous glucose monitor derived time in range and glycaemic variability with diet lifestyle and demographics.
    Kate M Bermingham, Harry A Smith, Emma L Duncan, Javier T Gonzalez, Ana M Valdes, Paul W Franks, Linda Delahanty, Hassan S Dashti, Richard Davies, George Hadjigeorgiou, Jonathan Wolf, Andrew T Chan, Tim D Spector, Sarah E Berry.
      Continuous glucose monitors (CGMs) provide detailed glucose profiles, but their relevance to health outcomes in individuals without diabetes remains unclear. Here we assess time in range (TIR3.9-5.6 and TITR3.9-7.8) and glycaemic variability in individuals (N = 3,634; age 46 ± 12 y; 83% female; BMI 27 ± 6 kg/m²) from PREDICT 1 (NCT03479866), PREDICT 2 (NCT03983733), and PREDICT 3 (NCT04735835) without diabetes or prediabetes, and explore associations with demographic, diet, lifestyle, cardiometabolic markers, and predicted cardiovascular risk. Outcomes are non-pre-defined exploratory analyses. Higher TIR3.9-5.6 is associated with lower HbA1c, OGTT glucose, carbohydrate intake, and higher protein intake. Sleep duration is inversely correlated with mean glucose. TIR3.9-5.6 provided moderate discrimination for predicted ASCVD 10-year risk (AUC = 0.75). While CGM metrics show potential to capture some components of glycaemic physiology, longer-term health outcomes are required to demonstrate whether CGM monitoring has utility for health management in euglycaemic individuals.
    DOI:  https://doi.org/10.1038/s41467-026-70308-3
  3. Nat Immunol. 2026 Mar 24.
    Commensals join the effector game.
    Julia Sanchez-Garrido.
      
    DOI:  https://doi.org/10.1038/s41590-026-02467-w
  4. Nature. 2026 Mar 25.
    Charting the human brain's lifelong functional organization.
    Richard A I Bethlehem, Daniel S Margulies.
      
    Keywords:  Brain; Imaging; Neuroscience
    DOI:  https://doi.org/10.1038/d41586-026-00637-2
  5. Nat Metab. 2026 Mar;8(3): 587-603
    PLIN5 phosphorylation orchestrates mitochondria lipid-droplet coupling to control hepatic lipid flux and steatosis.
    Sun Woo Sophie Kang, Lauryn A Brown, Colin B Miller, Katherine M Barrows, Jihye L Golino, Hanyang Liu, Constance M Cultraro, Daniel Feliciano, Mercedes B Cornelius-Muwanuzi, Kirsten Remmert, Jonathan M Hernandez, Andy D Tran, Michael Kruhlak, Alexei Lobanov, Maggie Cam, Natalie Porat-Shliom.
      Steatotic liver disease is common, yet the mechanisms by which hepatocytes cope with surges in dietary fatty acids remain unclear. Here we use single-cell tissue imaging (scPhenomics) and spatial proteomics to map lipid handling across dietary states. Fasting remodeled mitochondria and lipid droplets (LDs), increasing mitochondria-LD contacts, whereas contacts were infrequent in Western diet (WD)-fed male mice. Fasting also elevated perilipin-5 (PLIN5), a mediator of mitochondria-LD tethering. PLIN5 overexpression modulated contact formation in a phosphorylation-dependent manner: the S155A variant enhanced organelle contacts and LD expansion, whereas the S155E variant reduced contacts and yielded fewer, smaller LDs. Overexpression of the S155A variant in WD reduced lipotoxicity. These data reveal an adaptive organelle-interaction program that channels lipids during nutrient stress and is attenuated by an obesogenic diet. Our work establishes scPhenomics for spatially resolved cell-state analysis and identifies PLIN5 phosphorylation as a lever to tune hepatocyte lipid flux, suggesting therapeutic potential for targeting mitochondria-LD coupling.
    DOI:  https://doi.org/10.1038/s42255-026-01476-1
  6. Nat Immunol. 2026 Mar 25.
    A transcriptomic microglia taxonomy across mouse and human pathologies.
    Chintan Chhatbar, Roman Sankowski, Michael Schulz, Takashi Shimizu, Marius Schwabenland, Ori Staszewski, Christian Scheiwe, Stefan Nessler, Katharina Borst, Anaelle Aurelie Dumas, Ella Trost, Daniel Berchtold, Wesley Brandão, Omar Mossad, Adrià Dalmau Gasull, Maximilian Frosch, Daniel Erny, Martin Diebold, Elena Guffart, Katharina Ternka, Mihaela Guranda, Janaki Manoja Vinnakota, Marina Friesen, Koliane Ouk, Inken Waltl, Michael LaMorte, Timothy R Hammond, Giovanni Di Liberto, Ilena Vincenti, Mario Kreutzfeldt, Ibrahim T Mughrabi, Yousef Al-Abed, Thomas Blank, Melanie Meyer-Luehmann, Yanick J Crow, Nellwyn Hagen, Dimitry Ofengeim, Robert Zeiser, Matthias Kettwig, Jutta Gärtner, Andreas Meisel, Martin Schwemmle, Ulrich Kalinke, Jürgen Beck, Bertram Bengsch, Robert Thimme, Oleg Butovsky, Tamara Seredenina, Richard M Ransohoff, Francisco J Quintana, Katrin Kierdorf, Doron Merkler, Christine Stadelmann, Josef Priller, Marco Prinz.
      Single-cell studies have revealed substantial microglial diversity in development, homeostasis and disease. However, a framework enabling comparison and stratification of microglial states across contexts is needed. Here we generated an atlas of myeloid cell states by single-cell RNA sequencing more than one million central nervous system cells from more than 30 physiological and pathological conditions. This atlas enables us to establish a comprehensive taxonomy of myeloid cell states across brain disorders and related mouse models, comprising 27 superclusters and 192 clusters that are prevalent across diseases and largely conserved. We augment this taxonomic framework with spatial transcriptomics to map how immune cell states are organized within tissue and interact with their local cellular environment. Using in vivo perturbations, we also show that activation-associated microglial states are dependent on interferon and colony-stimulating factor 1 receptor signaling. Together, these findings provide a spatially aware taxonomic framework for central nervous system immune cells in health and disease.
    DOI:  https://doi.org/10.1038/s41590-026-02472-z
  7. Nature. 2026 Mar;651(8107): 856
    How the war in Iran is reshaping the energy landscape.
    Aisha Al-Sarihi.
      
    Keywords:  Energy; Government; Sustainability
    DOI:  https://doi.org/10.1038/d41586-026-00932-y
  8. Sci Transl Med. 2026 Mar 25. 18(842): eaed3762
    Beyond bystanders: How β cell stress shapes the autoimmune response in T1D.
    Feyza Engin, Decio L Eizirik.
      For many years, research focused on the immune system's role in the development of type 1 diabetes (T1D). However, mounting evidence suggests a critical involvement of intrinsic pancreatic β cell defects, particularly impaired cellular stress responses, in disease pathology. This shift in understanding is supported by the limited effectiveness of immune-targeting therapies, which have so far managed to delay, rather than prevent or cure, T1D. Here, we discuss why the immune system specifically targets β cells, how stress pathways modify the interaction between β cells and immune cells, β cell resilience, and challenges and opportunities in targeting β cell stress in T1D.
    DOI:  https://doi.org/10.1126/scitranslmed.aed3762
  9. Nat Metab. 2026 Mar 26.
    Atlas of one-carbon metabolism in conventional and germ-free mice reveals folate as a key determinant of biochemical pathways.
    Jonathan Williams, Woo Sung Kim, Rebecca Danner, Juyeong Cho, Bianca F Silva, David A Harris, Federico E Rey, Snehal N Chaudhari.
      Folates participate in the one-carbon metabolism (OCM) cycle, supporting many biochemical pathways. Existing methods to profile folate are limited in the diversity of vitamers they measure and the samples they profile. Here we present a metabolomics workflow for stable extraction, separation and measurement of folates, along with precursors and products of OCM-associated pathways. We profile these metabolites in 37 mouse tissues to chart an interactive 'OCM atlas' ( https://chaudharilab.com/folate-atlas/ ), revealing vast heterogeneity across organs and an uncharacterized folate derivative. We discover that, in adult mice, the gut microbiota is a consumer of folate and folate polyglutamylation in the host is not regulated by folate availability. Germ-free mice show tissue-specific shifts in methyl donor abundances relative to conventionally raised mice, indicative of altered DNA methylation. Correlation analyses uncover the central roles of folates in potentially modulating other biochemical pathways in tissues, thus linking microbial folate consumption directly to its global impacts on host metabolism.
    DOI:  https://doi.org/10.1038/s42255-026-01489-w
  10. Nature. 2026 Mar 25.
    Parasites trigger epithelial cell crosstalk to drive gut-brain signalling.
    Kouki K Touhara, Jinhao Xu, Joel Castro, Hong-Erh Liang, Guochuan Li, Mariana Brizuela, Andrea M Harrington, Sonia Garcia-Caraballo, Tracey O'Donnell, Daniel Neumann, Nathan D Rossen, Fei Deng, Gudrun Schober, Yulong Li, Richard M Locksley, Stuart M Brierley, David Julius.
      Parasitic infections modulate both immune and sensory responses, but how these systems collaborate to elicit protective behaviours remains incompletely understood. The gut epithelium contains specialized sensory cells that detect pathogens and irritants. These include cholinergic tuft cells, which sense parasites and initiate type 2 immune responses1-3, as well as serotonergic enterochromaffin (EC) cells, which detect irritants and communicate with afferent nerve fibres to transmit nociceptive signals4-6. Here we show that paracrine signalling between these cells constitutes a mechanism for neuro-immune interaction and gut-brain communication. We find that tuft cells use two distinct mechanisms of acetylcholine (ACh) release despite lacking synaptic vesicles and excitable membranes. These include acute release in response to parasite-derived metabolites, followed by constitutive 'leak-like' release, which occurs with type 2 inflammation. Although both mechanisms can activate muscarinic receptors on crypt-residing EC cells, only the sustained mode of ACh release elicits levels of serotonin sufficient to stimulate vagal afferent neurons that suppress food intake. This two-phase paracrine signalling mechanism explains how parasitic infection progresses from an initial asymptomatic phase to symptomatic established disease, in which type 2 immune and sensory signalling pathways within the gut-brain axis collaborate to evoke protective behaviours.
    DOI:  https://doi.org/10.1038/s41586-026-10281-5
  11. Nat Commun. 2026 Mar 21.
    In vivo metabolic tagging and targeting of circulating red blood cells.
    Yusheng Liu, Yizun Wang, Kyungwon Ko, Yuan Liu, Haiyi Huang, Yueji Wang, Jiadiao Zhou, Dhyanesh Baskaran, Joonsu Han, Rimsha Bhatta, Daniel Nguyen, Cecilia Leal, Matthew R Berry, Fan Lam, Hua Wang.
      Engineering red blood cells (RBCs) has been widely explored for drug delivery, imaging, vaccination, and other applications. However, effective strategies to directly engineer RBCs in vivo are still lacking. Here, we report successful metabolic glycan labeling of RBCs in vivo. We demonstrate that systemically administered azido-sugars can metabolically label circulating RBCs with azido groups, through labeling of both mature RBCs and RBC precursor cells. The surface azido tags on RBCs can persist for over 42 days in female mice (nearly the lifespan of RBCs), while tags on leukocytes decay to negligible levels within 3 days. Azido-labeled RBCs can covalently capture dibenzocyclooctyne-bearing cargos in vivo via click chemistry, extending cargo circulation from hours to over 35 days. This RBC tagging and targeting technology can improve fluorescence imaging of blood vessels, enable long-term MRI of brain vasculatures with a single gadolinium dose, and improve the pharmacokinetics of drugs.
    DOI:  https://doi.org/10.1038/s41467-026-71013-x
  12. Lancet Diabetes Endocrinol. 2026 Mar 20. pii: S2213-8587(25)00424-3. [Epub ahead of print]
    Revisiting the burden and patterns of myocardial infarction in type 1 diabetes.
    Angelo Avogaro, Gian Paolo Fadini.
      
    DOI:  https://doi.org/10.1016/S2213-8587(25)00424-3
  13. Nat Cardiovasc Res. 2026 Mar 24.
    Cardiovascular PIEZO discovery continues apace to reveal myocardial nerves feeling posture and blood loss.
    David J Beech.
      
    DOI:  https://doi.org/10.1038/s44161-026-00802-w
  14. Science. 2026 Mar 26. 391(6792): eadz6830
    Distinctive DNA sequence features define epigenetic longevity of inflammatory memory.
    Christopher J Cowley, Sairaj M Sajjath, Luis F Soto-Ugaldi, Mara Steiger, Samantha B Larsen, Thomas Carroll, Douglas Barrows, Alexandra Mattei, Kevin A U Gonzales, Wei Wang, Kevin Li, Alexander Meissner, Helene Kretzmer, Dana Pe'er, Elaine Fuchs.
      Tissues harbor memories of inflammation, which heighten sensitivity to diverse future assaults. Whether and how these adaptations are sustained through time and cell division remain poorly understood. We show that in mice, epidermal stem cells store lifelong, functional epigenetic records of psoriasis-like skin flares. Applying deep learning to investigate these chromatin dynamics, we unearth CpG dinucleotide density as a major driver of memory persistence. Although unnecessary for inflammation-induced transcription factors to open and establish memories, CpG-enriched sequences thereafter become essential, reinforcing accessibility across cellular generations by integrating DNA demethylation, methylation-sensitive transcription factors, sequence-intrinsic nucleosome disaffinity, and the nucleosome-destabilizing histone variant H2A.Z. Thus, once activated by inflammation-induced transcription factors, DNA sequences orchestrate persistent poise, imparting long-lasting memory to stress-sensitive genes and profoundly affecting tissue fitness upon recall.
    DOI:  https://doi.org/10.1126/science.adz6830
  15. Nature. 2026 Mar 27.
    Motherhood derails women's academic careers - these data reveal how and why.
    Diana Kwon.
      
    Keywords:  Careers; Economics
    DOI:  https://doi.org/10.1038/d41586-026-00981-3
  16. Cell Metab. 2026 Mar 23. pii: S1550-4131(26)00087-2. [Epub ahead of print]
    The many pathways driving liver inflammation in MASH.
    Herbert Tilg, Timon E Adolph, Stefano Romeo, Rohit Loomba.
      Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting one-third of the global population. Most patients exhibit simple steatosis, whereas up to 20% develop metabolic dysfunction-associated steatohepatitis (MASH), potentially culminating in liver cirrhosis and hepatocellular carcinoma. Diverse parallel mechanisms contribute to the development of MASH, which are fueled by hepatic lipotoxicity, intestinal dysbiosis, and pro-inflammatory diets shaping innate and adaptive immune responses. Moreover, adipose tissue is driving systemic inflammation in obesity, contributing to the inflammatory burden in obesity-related MASH. Polygenetic and multiomic risk scores identify distinct types of MASLD with dominant aggressive liver disease or extrahepatic cardiometabolic disease. Here, we review the complexity of multiple parallel inflammatory hits in MASH and delineate that most current MASH drugs exert pleiotropic metabolic and anti-inflammatory properties. These new therapies will change the clinical management of this disease in the near future.
    Keywords:  cytokines; fibrosis; inflammation; metabolism dysfunction-associated steatotic liver disease
    DOI:  https://doi.org/10.1016/j.cmet.2026.02.018
  17. Sci Immunol. 2026 Mar 27. 11(117): eaeb1459
    Palmitate-induced mitochondrial damage restricts histone acetylation in CD8 T cells to impair antitumor immunity.
    Silvia Tiberti, Sara Gennari, Martina Romeo, Ilir Sheraj, Mohamed Faisal Kassir, Juan Fernández-García, Carina B Nava Lauson, Roberta Noberini, Carlotta Catozzi, Tiziano Dallavilla, Mattia Ballerini, Alessia Loffreda, Simona G Codreanu, Stacy D Sherrod, Katrina L Leaptrot, Alexandra C Schrimpe-Rutledge, John A McLean, Martin H Schaefer, Simona Rodighiero, Tiziana Bonaldi, Sarah-Maria Fendt, Besim Ogretmen, Sara Sdelci, Luigi Nezi, Teresa Manzo.
      Lipid accumulation in the tumor microenvironment is a hallmark of solid tumors, with increased palmitate (PA) availability fostering tumor progression. Although PA's direct effects on cancer cells are well described, its impact on CD8 T cells [cytotoxic T lymphocytes (CTLs)] remains unclear. Here, we show that PA irreversibly impairs CTL mitochondrial metabolism, leading to the loss of effector functions and compromised antitumor immunity. PA-induced mitochondrial dysfunction reduced histone acetylation and chromatin accessibility, suppressing transcription of genes involved in T cell replication and effector programs. We identified sphingosine kinase 2 (SPHK2) as a key mediator of PA-induced dysfunction, with pharmacological inhibition of SPHK2 restoring mitochondrial fitness, rescuing CTL effector function, and promoting antitumor activity. These findings uncover a distinct mechanism by which PA drives immune evasion in tumors and highlight SPHK2 as a potential therapeutic target to enhance T cell-based immunotherapies.
    DOI:  https://doi.org/10.1126/sciimmunol.aeb1459
  18. Nat Metab. 2026 Mar;8(3): 527-528
    The expanding role of mitochondria-lipid droplet contacts in liver and their disruption by MASLD.
    Jessica Segalés, Marc Liesa.
      
    DOI:  https://doi.org/10.1038/s42255-026-01483-2
  19. Cell Rep. 2026 Mar 20. pii: S2211-1247(26)00204-4. [Epub ahead of print]45(4): 117126
    Aging disrupts sympathetic innervation of the thymus.
    Randall S Carpenter, Farzana Begum, Maria K Lagou, Mahamudun Bhuiyan, Hillary Guzik, Vera DesMarais, George S Karagiannis, Maria Maryanovich.
      The thymus, a primary lymphoid organ essential for lifelong T cell development, undergoes progressive age-related involution. The thymus is innervated by the sympathetic nervous system (SNS), but the extent of innervation and its relationship to the microenvironment or age-related involution remain unclear. Here, we provide a detailed mapping of thymic sympathetic innervation using advanced imaging methods to characterize its distribution and relationship with vascular structures, capsule, and stromal compartments. In contrast to previous studies, we provide direct evidence that aging leads to profound deterioration of thymic sympathetic innervation. Age-associated axonal degeneration in the thymus includes collapsing of axon-vascular structures, reduced axonal volume, nerve fiber fraying, and loss of axonal synapses. We also demonstrate that sympathectomy impairs thymic homeostasis, whereas sympathomimetic treatment enhances its function in aged mice. Our findings challenge the paradigm of age-related increase in thymic innervation, establishing the SNS as an underappreciated regulator of thymic function and aging.
    Keywords:  CP: immunology; CP: neuroscience; immune aging; neuroimmunology; sympathetic nervous system; thymic innervation; thymic microenvironment; thymopoiesis; thymus; tissue clearing; whole-tissue imaging; β-adrenergic signaling
    DOI:  https://doi.org/10.1016/j.celrep.2026.117126
  20. Cell Metab. 2026 Mar 24. pii: S1550-4131(26)00093-8. [Epub ahead of print]
    Mitochondrial lactate venting limits oxidative stress.
    Daniela Rauseo, Yasna Contreras-Baeza, Mildreth Salazar, Abigail J Galarza, Sebastián Holtheuer-Gallardo, Hugo Faurand, Natali Cárcamo-Lemus, Raibel Suárez, Joel L Asenjo, Alexandra von Faber-Castell, Franco Silva, Valentina Mora-González, Jan Dernic, Luca Ravotto, Matthias T Wyss, Felipe Baeza-Lehnert, Iván Ruminot, Carlos Alvarez-Navarro, Alejandro San Martín, Bruno Weber, Pamela Y Sandoval, L Felipe Barros.
      Lactate has been proposed to enter mitochondria and fuel respiration, but this "intracellular lactate shuttle" remains controversial. Using genetically encoded lactate and redox sensors in cultured cells and neurons in vivo, we identify a dynamic lactate pool within the mitochondrial matrix that tracks extracellular and blood lactate and promotes lactylation of mitochondrial proteins. Lactate crosses the inner mitochondrial membrane through a saturable pathway that is partly sensitive to pharmacologic and genetic inhibition of the mitochondrial pyruvate carrier (MPC). Despite transport and matrix lactate dehydrogenase activity, lactate does not measurably energize the electron transport chain under the conditions tested. Instead, energized mitochondria can produce lactate from pyruvate, a response enhanced by hypoxia. Blocking MPC causes matrix lactate and H₂O₂ accumulation, revealing a rapid lactate-based "vent" that modulates matrix energy and reactive oxygen species.
    Keywords:  genetically encoded fluorescent indicator; hypoxia; lactate; lactate dehydrogenase; membrane transport; metabolism; mitochondrial pyruvate carrier; monocarboxylate transporter; pyruvate; reactive oxygen species
    DOI:  https://doi.org/10.1016/j.cmet.2026.02.020
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