bims-nimamd Biomed News
on Neuroimmunity and neuroinflammation in ageing and metabolic disease
Issue of 2026–09–13
fourteen papers selected by
Fawaz Alzaïd, Sorbonne Université
  1. Clues to immune havoc in the brain.
  2. Childhood proteomic signatures that predict adult cardiometabolic disease.
  3. Macrophages tune NK cell IFNγ production through direct lipid transfer.
  4. Chromatin triggers tissue-specific immunity in 3D.
  5. Spatial and functional specialization of human splenic innate lymphoid cells.
  6. The complete telomere-to-telomere sequence of a mouse Y chromosome.
  7. Drug delivery gets subcellular.
  8. Why the super-fun Ig Nobel prizes bring serious value to science.
  9. The hidden role of the bone marrow in Alzheimer's disease.
  10. Aging rises, yet the double burden of illness remains.
  11. Multi-ancestry genetic architecture of heart failure subtypes.
  12. Limited Early-Life Sugar Intake Linked to Lower Dementia Risk.
  13. Artery tertiary lymphoid organs encode a pathogenic high-affinity autoantibody-autoantigen pair in atherosclerosis.
  14. Rab4b controls hepatic glucose production during fasting through glycophagy.
  1. Science. 2026 09 10. 393(6816): 1070-1071
    Clues to immune havoc in the brain.
    Jennie Erin Smith.
      Study in mice strengthens T cells' ties to neurodegenerative conditions like Alzheimer's.
    DOI:  https://doi.org/10.1126/science.aem2422
  2. Nat Metab. 2026 Sep 11.
    Childhood proteomic signatures that predict adult cardiometabolic disease.
      
    DOI:  https://doi.org/10.1038/s42255-026-01588-8
  3. Nat Commun. 2026 Aug 08. pii: 9527. [Epub ahead of print]17(1):
    Macrophages tune NK cell IFNγ production through direct lipid transfer.
    Cathal Keane, Shauna Mayock, Carrie Corkish, Ella Rogerson, Cristhiane Favero de Aguiar, Ya Gao, Sarah Kenny, Lorraine Brennan, Suzanne M Cloonan, David K Finlay.
      Natural killer (NK) cells are critical effectors of innate immunity, but their activity is strongly influenced by metabolic state. While intrinsic NK metabolism has been studied extensively, less is known about how surrounding immune cells shape NK cell function. Here, we identify a direct metabolic communication axis between macrophages and NK cells. Using co-culture and in vivo models, we show that lipopolysaccharide-stimulated macrophages induce lipid accumulation in NK cells that suppresses mTORC1 activity and the production of IFNγ. This lipid accumulation is visualised as increased lipid droplets content in NK cells, generated using fatty acids synthesised within the macrophages. Genetic and pharmacological approaches show that fatty acid transfer from macrophages to NK cells requires cell-cell contact and is associated with CD36 protein transfer via trogocytosis. Blocking fatty acid synthesis specifically in macrophages prevents lipid accumulation in NK cells and restores both mTORC1 activity and IFNγ production. These findings define a previously unrecognized mechanism of macrophage-NK cell cross-regulation, revealing how metabolic exchange constrains NK effector function and establishing a feedback circuit with implications for hyperinflammation and immunotherapy.
    DOI:  https://doi.org/10.1038/s41467-026-76444-0
  4. Immunity. 2026 Sep 08. pii: S1074-7613(26)00347-X. [Epub ahead of print]59(9): 2354-2357
    Chromatin triggers tissue-specific immunity in 3D.
    Joshua McKeever, Andrew S Koh.
      Antigenic and environmental stimuli sensed by innate and adaptive immune cells trigger cognate functions that allow the coordination of the appropriate immune response. In this issue of Immunity, Tzerpos et al. and Jay et al. demonstrate that chromatin architecture dynamics integrate sensory inputs with functional outputs to regulate and direct immune cell responses.
    DOI:  https://doi.org/10.1016/j.immuni.2026.08.010
  5. Nat Commun. 2026 08 11. pii: 9631. [Epub ahead of print]17(1):
    Spatial and functional specialization of human splenic innate lymphoid cells.
    Sarah J Colpitts, Sinthuja Jegatheeswaran, Siavash Mashhouri, Ash Hagerman, Mahmoud El-Maklizi, Humaira Murshed, Martin L Mak, Kyle T Reid, Julia M Murphy, Jessica A Mathews, Clinton S Robbins, Sarah Q Crome.
      Secondary lymphoid organs, including the spleen, integrate innate and adaptive immune responses. Studies in murine models and humans highlight Natural Killer (NK) cells and other innate lymphoid cells (ILC) as key organizers of splenic immune activity, yet their in situ organization and interactions within immune networks are incompletely understood. Here, we report a spatially resolved single-cell atlas of human splenic NK cells and ILCs. We identify CD39+TIGIT+CD56bright NK cells that localize with alternatively activated macrophages outside of B cell follicles. Splenic ILC2s, enriched in vascular-associated regions, express CD40L and can promote B cell survival and IgA secretion. Finally, we define three spatially and functionally distinct ILC3 subsets, namely KLF2⁺ progenitor-like ILC3s, follicle-associated CD38⁺ ILC3s, and IFNGR1⁺ ILC3s, that can promote B cell proliferation, IL-10 production, and IgG class switching. This spatially resolved atlas provides a comprehensive reference of human splenic ILC organization, specialization, and interaction networks.
    DOI:  https://doi.org/10.1038/s41467-026-76100-7
  6. Science. 2026 Sep 10. 393(6816): eaea2249
    The complete telomere-to-telomere sequence of a mouse Y chromosome.
    Qilin Li, Junli Liu, Si Chen, Yixuan Hu, Dengfeng Li, Zhuojie Su, Yanxiao Zhang, Xiaochun Yu.
      The mouse Y chromosome is essential for male reproduction, yet the GRCm39 reference contains 25 gaps, particularly in repetitive and complex regions. Here, we assembled a telomere-to-telomere Y chromosome (mT2T Y) of 95.21 Mb from a C57BL/6 mouse incorporating parental genomes. This assembly fills all gaps, corrects structural errors, and adds over 8.70 Mb of previously unassembled sequence to the reference genome. We annotated 142 previously unidentified genes, identified Y specific satellite arrays, and mapped homologous recombination loci in the pseudoautosomal region (PAR). Analysis of X Y homologous gene expression revealed a Y chromosome dosage compensation mechanism. By combining mT2T Y with T2T mhaESC, we completed the T2T assembly of all C57BL/6 chromosomes, designated T2T mhaESC+Y, providing a complete C57BL/6 reference genome.
    DOI:  https://doi.org/10.1126/science.aea2249
  7. Nature. 2026 Sep;657(8131): S14-S15
    Drug delivery gets subcellular.
    Katherine Bourzac.
      
    Keywords:  Cell biology; Therapeutics
    DOI:  https://doi.org/10.1038/d41586-026-02659-2
  8. Nature. 2026 Sep;657(8131): 319
    Why the super-fun Ig Nobel prizes bring serious value to science.
      
    Keywords:  Careers; Publishing; Scientific community
    DOI:  https://doi.org/10.1038/d41586-026-02793-x
  9. Nat Neurosci. 2026 Sep 08.
    The hidden role of the bone marrow in Alzheimer's disease.
      
    DOI:  https://doi.org/10.1038/s41593-026-02418-6
  10. Nat Aging. 2026 Sep 07.
    Aging rises, yet the double burden of illness remains.
    Joseph L Dieleman.
      
    DOI:  https://doi.org/10.1038/s43587-026-01218-8
  11. Nat Commun. 2026 Aug 13. pii: 9730. [Epub ahead of print]17(1):
    Multi-ancestry genetic architecture of heart failure subtypes.
    VA Million Veteran Program
      Heart failure (HF) affects 6.7 million people in the US and includes two major subtypes, HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), with distinct genetic architectures. We meta-analyze genome-wide association studies (GWAS) of 38,781 HFrEF cases, 38,163 HFpEF cases, and 526,135 controls across European, African, Hispanic, and Asian ancestries using the Million Veteran Program and Vanderbilt University DNA Databank (BioVU). We identify 46 genome-wide significant loci for HFrEF (9 novel) and 3 loci for HFpEF (1 novel). Four HFrEF loci are detected in African ancestry participants near CD36, SPI1, TRIM48, and SPNS3, with lead SNPs showing low risk-allele frequencies in European populations. In the all-cause HF meta-analysis (200,070 cases, 2,076,466 controls), we identify 136 loci (12 novel). Gene-based tests, tissue enrichment, transcriptome-wide association, and fine-mapping implicate vascular, metabolic, and TGF-β/Smad signaling pathways and nominate candidate causal genes, clarifying shared and subtype-specific risk across ancestries.
    DOI:  https://doi.org/10.1038/s41467-026-76438-y
  12. JAMA. 2026 Sep 11.
    Limited Early-Life Sugar Intake Linked to Lower Dementia Risk.
    Anna Bock.
      
    DOI:  https://doi.org/10.1001/jama.2026.14716
  13. Nat Cardiovasc Res. 2026 Sep;5(9): 869-890
    Artery tertiary lymphoid organs encode a pathogenic high-affinity autoantibody-autoantigen pair in atherosclerosis.
    Chuankai Zhang, Xi Zhang, Yi Ran, Zhihua Wang, Liping Li, Shu Wang, Junjie Zheng, Yixin Zhang, Ting Sun, Yutao Li, Shu Lu, Mingyang Hong, Zhe Ma, Sabine Steffens, Michael Hristov, Xavier Blanchet, Jingpu Zhu, Xinwen Dou, Xinyi Deng, Klaus Dornmair, Desheng Hu, Shibojyoti Lahiri, Axel Imhof, Nadja Sachs, Lars Maegdefessel, Jingyi Xiao, Jianning Zhang, Yan Wang, Hua Hong, Livia Habenicht, Xinyu Weng, Junbo Ge, Christian Weber, Donato Santovito, Rachael Bashford-Rogers, Sarajo K Mohanta, Klaus Ley, Andreas J R Habenicht, Changjun Yin.
      Artery tertiary lymphoid organs (ATLOs) emerge in atherosclerosis, which is a chronic inflammatory artery disease with an autoimmune component. However, whether disease-relevant autoimmune B cells emerge in ATLOs remains unknown. In this study, we isolate germinal center (GC) B cells from ATLOs and lymph nodes from healthy and atherosclerosis-burdened mice, expression clone 60 autoantibodies and screen them for arterial wall reactivity. ATLO GC B cell-derived autoantibodies skew to atherosclerosis-relevant autoantigens versus their counterparts in lymph nodes of both genotypes. One ATLO GC B cell-derived autoantibody (termed A6) binds to histone 2B (H2B) with high affinity. Both vaccination with H2B and adoptive transfer of A6 accelerate atherosclerosis, revealing a pathogenic autoantibody-autoantigen pair. Mechanistically, ATLOs specifically show both distorted B cell activation and immune tolerance checkpoint-regulating gene expression profiles. In a human cohort, circulating anti-H2B antibody titers positively correlate with aortic calcification in humans. We suggest that ATLOs harbor a dysregulated immune tolerance environment permissive for autoreactive B cells that express pathogenic autoantibodies promoting atherosclerosis.
    DOI:  https://doi.org/10.1038/s44161-026-00864-w
  14. Nat Commun. 2026 Aug 10. pii: 9587. [Epub ahead of print]17(1):
    Rab4b controls hepatic glucose production during fasting through glycophagy.
    Marion Dussot, Lucie Le Parc, Sihame Sabbane, Alycia Zedda, Abderrahman Chafik, Alexandre Gallerand, Karine Dumas, Stéphanie Bonnafous, Yun Kwon, Sandra Lacas-Gervais, Charlotte Hinault Boyer, Giulia Chinetti, Sophie Giorgetti-Peraldi, Philippe Gual, Stoyan Ivanov, Anja Zeigerer, Jean-François Tanti, Mireille Cormont, Jerome Gilleron.
      Hepatic glucose production, essential for maintaining glycemia, is often altered in metabolic-associated fatty liver and glycogen storage diseases. Therefore, understanding the mechanisms that regulate the glucose production by hepatocyte is pivotal. Recent studies have identified endocytic trafficking as a key modulator of liver glucose production. Particularly, its role in directing protein trafficking toward lysosomal degradation influences gluconeogenesis. However, the contribution of endocytic recycling to liver glucose production remains yet poorly understood. Here, we demonstrate that hepatocyte-specific disruption of endocytic recycling, achieved through Rab4b knockout in male, leads to fasting hyperglycemia. Mechanistically, hepatocytes lacking Rab4b exhibit an increased capacity to produce glucose independently of gluconeogenesis by depleting their glycogen stores. This is driven by enhanced glycophagy, leading to excessive glucose release and fasting hyperglycemia. Notably, liver Rab4b expression also correlates with glycemia in both mice and human, highlighting a critical role of Rab4b-dependent endocytic recycling in regulating blood glucose homeostasis during fasting.
    DOI:  https://doi.org/10.1038/s41467-026-76218-8
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