bims-nimamd Biomed News
on Neuroimmunity and neuroinflammation in ageing and metabolic disease
Issue of 2026–06–21
fifteen papers selected by
Fawaz Alzaïd, Sorbonne Université
  1. Why regulatory T cells fail to control inflammation in rheumatoid arthritis.
  2. Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases.
  3. The brain region that could provide a cognitive 'reservoir' in old age.
  4. Blood signatures of cell type-specific aging forecast disease risk and resilience.
  5. Understanding the somatic evolution of metabolic traits.
  6. Hematopoietic somatic mutations in atherosclerotic cardiovascular disease.
  7. An aminoacyl-tRNA synthetase governs dsRNA-mediated trade-off between longevity and innate immunity.
  8. Ultraprocessed Foods Linked to Cardiometabolic Risks.
  9. How do researchers choose what to work on?
  10. BMI-genome interactions regulate global gene expression with emphasis in brain and gut.
  11. EasySCP unveils extensive liver zonation at single-cell proteomics resolution.
  12. Whole blood epigenomic and transcriptomic characterization identifies vulnerable molecular subtypes of chronic coronary disease.
  13. Bacterial infection reshapes monocyte and macrophage ontogeny at the CNS borders.
  14. Nuclear STING compromises replication fidelity.
  15. Immune responses in aging adults.
  1. Nat Immunol. 2026 Jun 18.
    Why regulatory T cells fail to control inflammation in rheumatoid arthritis.
      
    DOI:  https://doi.org/10.1038/s41590-026-02546-y
  2. Nat Immunol. 2026 Jun 16.
    Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases.
    Accelerating Medicines Partnership (AMP) RA/SLE Network
      Regulatory T cells (Treg cells), characterized by FOXP3 expression, maintain immune homeostasis, but their function is impaired in autoimmune diseases such as rheumatoid arthritis (RA). Here we used single-cell RNA sequencing to analyze Treg cells in synovial tissues from patients with RA. We identified two predominant Treg states, CD25hiCXCR6pos Treg cells and dysfunctional CD25loAREGpos Treg cells, both enriched in synovial tissues but not in blood. Cortisol, activated by fibroblasts, drove AREG expression and impaired suppressive function in CD25loAREGpos Treg cells, and AREG promoted an inflammatory phenotype in synovial fibroblasts. By contrast, CD25hiCXCR6pos Treg cells remained highly suppressive and were supported by membrane-bound tumor necrosis factor (TNF)-expressing macrophages. TNFR2 engagement prevented or reversed the dysfunctional Treg cell state. These two Treg cell subsets were also observed in juvenile idiopathic arthritis, indicating shared mechanisms across inflammatory arthritis. These findings define distinct pathways driving functional and dysfunctional Treg cell states in inflamed tissues and implicate potential therapeutic strategies.
    DOI:  https://doi.org/10.1038/s41590-026-02540-4
  3. Nature. 2026 Jun;654(8120): 845
    The brain region that could provide a cognitive 'reservoir' in old age.
      
    Keywords:  Neurodegeneration
    DOI:  https://doi.org/10.1038/d41586-026-01870-5
  4. Nat Med. 2026 Jun;32(6): 1985-1986
    Blood signatures of cell type-specific aging forecast disease risk and resilience.
      By measuring thousands of proteins in blood samples from over 60,000 people, we built molecular 'clocks' to estimate how fast cells age. Our analyses show that cell types age at different rates within the same person. Accelerated aging of specific cell types is associated with increased disease risk, whereas slower aging of others is linked to protection and improved survival.
    DOI:  https://doi.org/10.1038/s41591-026-04447-x
  5. Nat Metab. 2026 Jun 16.
    Understanding the somatic evolution of metabolic traits.
    Radhika Khandelwal, Anand Kumar Sharma.
      
    DOI:  https://doi.org/10.1038/s42255-026-01551-7
  6. Atherosclerosis. 2026 Jun;pii: S0021-9150(26)00084-5. [Epub ahead of print]417 120718
    Hematopoietic somatic mutations in atherosclerotic cardiovascular disease.
    Beatriz L Ramos-Neble, José J Fuster.
      Age-related somatic mosaicism in the hematopoietic system is increasingly recognized as a risk factor for atherosclerotic cardiovascular disease. The most prominent example is clonal hematopoiesis of indeterminate potential (CHIP), defined as the expansion of hematopoietic clones carrying acquired mutations in genes recurrently mutated in myeloid hematological malignancies, typically at a variant allele fraction ≥2%. Across large human cohorts, CHIP is associated with increased risk of coronary artery disease and other atherosclerosis-related outcomes, although the magnitude of the association varies substantially by mutated gene and clone size. Complementary experimental studies in hyperlipidemic mice support a causal contribution to atherosclerosis for several CHIP drivers and reveal mutation-specific inflammatory mechanisms. These mechanistic insights are beginning to inform the design of genotype-guided, anti-inflammatory prevention strategies. In parallel, loss of the Y chromosome (LOY), the most frequent somatic chromosomal alteration detected in blood in aging men, has been associated with myocardial infarction and adverse cardiovascular outcomes, yet its causal role in atherosclerosis remains unproven. Here, we summarize current evidence for CHIP and LOY as heterogeneous, mutation-dependent contributors to atherosclerotic cardiovascular disease, highlighting methodological considerations that influence the observed associations, and outlining key knowledge gaps that must be addressed to allow for clinical translation.
    DOI:  https://doi.org/10.1016/j.atherosclerosis.2026.120718
  7. Mol Cell. 2026 Jun 18. pii: S1097-2765(26)00322-9. [Epub ahead of print]86(12): 2237-2239
    An aminoacyl-tRNA synthetase governs dsRNA-mediated trade-off between longevity and innate immunity.
    Haruka Ozaki, Nobunari Sasaki, Shunsuke Kitajima.
      In this issue of Molecular Cell, Sohn et al.1 explore how endogenous dsRNAs influence organismal aging and identify an unexpected function of the aminoacyl-tRNA synthetase FARS-1/FARSA in regulating mitochondrial dsRNA homeostasis to balance longevity and innate immunity.
    DOI:  https://doi.org/10.1016/j.molcel.2026.05.016
  8. JAMA. 2026 Jun 18.
    Ultraprocessed Foods Linked to Cardiometabolic Risks.
    Samantha Anderer.
      
    DOI:  https://doi.org/10.1001/jama.2026.8312
  9. Nature. 2026 Jun 16.
    How do researchers choose what to work on?
      
    Keywords:  History; Nutrition; Scientific community
    DOI:  https://doi.org/10.1038/d41586-026-01811-2
  10. Cell Genom. 2026 Jun 18. pii: S2666-979X(26)00142-4. [Epub ahead of print] 101280
    BMI-genome interactions regulate global gene expression with emphasis in brain and gut.
    Rebecca Signer, Carina Seah, Hannah Young, Kayla Retallick-Townsley, Julia Ciarcia, Agathe De Pins, Alanna Cote, Seoyeon Lee, Meng Jia, Jessica Johnson, Keira J A Johnston, Jiayi Xu, Kristen J Brennand, Laura M Huckins.
      Genome-wide association studies identify single-nucleotide polymorphisms (SNPs) associated with disease in a population but do not reliably account for individual environmental effects, despite evidence that environment mediates SNP functional regulatory capacity. Body mass index (BMI) is associated with physiologic processes across disorders but hasn't been modeled as an environment for disease-associated SNPs. We use an interaction approach to identify SNPs that contextually regulate gene expression across the BMI spectrum, called BMI-dynamic expression quantitative trait loci (BMI-eQTL). We found BMI-eQTL across tissues, including brain and gut, while the main effects of BMI were confined to endocrine tissues. We demonstrate that cell type, putative enhancers, and/or inflammatory cytokines underlie BMI-eQTL. We develop models to predict gene expression using BMI-by-SNP interactions and identify more replicating disease-associated genes than SNP-only models. While neither genetics nor BMI is sufficient as a standalone measure to capture the complexity of downstream cellular consequences, including environment helps power disease gene discovery.
    Keywords:  BMI; eQTLs; functional genomics; genotype-environment interactions
    DOI:  https://doi.org/10.1016/j.xgen.2026.101280
  11. Nat Commun. 2026 Jun 16.
    EasySCP unveils extensive liver zonation at single-cell proteomics resolution.
    Bingbing Hao, Jinghui Wei, Jiaen Xu, Ying Fu, Qiaoyu Zou, Xu Wang, Siyu Wang, Yixuan Shi, Yale Chen, Ken Xie, Xun Huang, Tong-Jin Zhao, Zigang Dong, Peng Li, Guochen Qin, Ido Amit, Baoguo Li.
      The broader application of single-cell proteomics (SCP) in biology has been limited by complex workflows and reliance on specialized instrumentation. Here we present EasySCP, a high-throughput method that integrates FACS-based single-cell sorting, an all-in-one, single-step digestion process in 384-well plates, and sensitive mass spectrometry. EasySCP identifies nearly 5000 proteins from individual HEK293 cell. Applied to female murine liver, EasySCP achieves spatially informed proteomics profiling of hepatocytes zonation, detecting an average of 3500 proteins per hepatocyte and uncovering zonation patterns for 3277 out of 5267 proteins. Building on 215 conserved zonation markers, we further develop hepatocyte spatial status score (HSS) that enables reconstruct liver zonation across single-cell and multi-omics datasets. Together, our study introduces EasySCP, a broadly accessible tool for dissecting cellular heterogeneity at single-cell proteomics resolution in both healthy and disease states, effectively bridging the gap between transcriptomics and functional proteomics.
    DOI:  https://doi.org/10.1038/s41467-026-74525-8
  12. Nat Commun. 2026 Jun 16.
    Whole blood epigenomic and transcriptomic characterization identifies vulnerable molecular subtypes of chronic coronary disease.
    ISCHEMIA Biorepository Research Group
      Chronic coronary disease (CCD) remains a leading cause of morbidity and mortality worldwide. However, current clinical assessments, including tests of inducible ischemia or coronary artery disease severity poorly discriminate risk for future cardiovascular (CV) disease events among this population with established CCD. To address this gap, our study leverages high-dimensional molecular data from the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) Trials biorepository to molecularly characterize patients with CCD. By integrating transcriptomic (N = 646) and methylomic (N = 732) data with core-lab confirmed clinical phenotyping, we describe molecular signatures associated with disease severity and identify distinct whole-blood molecular subtypes of CCD. These subtypes demonstrate differential risks of CV events, independent of traditional clinical risk scores, and have distinct molecular and immune profiles. Validation of the transcriptomic and methylomic subtypes in two independent external cohorts confirms the clinical relevance and generalizability of our findings. These findings underscore the potential of blood-based multi-omic approaches to refine risk stratification, improve personalized treatment strategies and advance secondary prevention in CCD. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT01471522; https://clinicaltrials.gov/ct2/show/NCT01471522.
    DOI:  https://doi.org/10.1038/s41467-026-73815-5
  13. Sci Immunol. 2026 Jun 19. 11(120): eaee9584
    Bacterial infection reshapes monocyte and macrophage ontogeny at the CNS borders.
    Vitka Gres, Florens Lohrmann, Vidmantė Fuchs, Jana Neuber, Zohreh Mansoori Moghadam, Anne K Lösslein, Lance F P Bosch, Tiago Figueiral-Martins, Sebastian Baasch, David Obwegs, Gianni Monaco, Julia Henschel, Klaus P Knobeloch, Marco Prinz, Steffen Jung, Katrin Kierdorf, Sagar, Julia Kolter, Daniel Erny, Philipp Henneke.
      Macrophages in the meninges contribute to immune defense of the central nervous system (CNS), yet their site-specific origin and function remain poorly understood. Using an intravenous model of streptococcal meningoencephalitis in mice, we found bacteria predominantly in the leptomeninges and dura. Nevertheless, monocyte infiltration into the leptomeninges and parenchyma strongly correlated with disease severity. In the dura, infection triggered activation and loss of resident macrophages, followed by rapid engraftment of inflammatory monocytes that transiently replenished the macrophage niche. Under homeostasis, dural monocytes were supplied CCR2 independently from adjacent skull bone marrow. During infection, this local source was insufficient, necessitating recruitment from peripheral bone marrow. Infection further reshaped monocyte ontogeny, increasing monocyte-dendritic cell progenitor-derived monocytes, which expressed higher major histocompatibility complex class II levels and persisted in the brain alongside CD4+ T cells during resolution. Together, these findings reveal dynamic, compartment-specific remodeling of monocyte recruitment and differentiation across CNS borders during bacterial meningoencephalitis.
    DOI:  https://doi.org/10.1126/sciimmunol.aee9584
  14. Nat Rev Immunol. 2026 Jun 15.
    Nuclear STING compromises replication fidelity.
    Marie-Therese A El-Daher, Yanick J Crow.
      
    DOI:  https://doi.org/10.1038/s41577-026-01324-z
  15. J Clin Invest. 2026 06 15. pii: e206227. [Epub ahead of print]136(12):
    Immune responses in aging adults.
    Cornelia M Weyand, Jörg J Goronzy.
      As a widely distributed network of cells, tissues, and organs, the human immune system is profoundly vulnerable to the effects of aging. Intrinsic and extrinsic stressors progressively erode its structural integrity and functional resilience, weakening core protective responses and increasing susceptibility to infection, malignancy, and tissue degeneration. At the same time, aging heightens the risk of chronic inflammation and autoimmune disease. Hematopoietic stem cells become uniquely compromised as aging intensifies metabolic and replicative stress. Their continuous high-volume turnover results in diminished self-renewal capacity, skewed lineage output, and dominance of expanded clones. These changes undermine innate immune competence and amplify inflammatory activity. Adaptive immune function declines with age through coordinated cellular and molecular programs. T and B lymphocytes exhibit a decline in naive cells, progressive loss of stemness, shortened lifespan, and constrained clonal diversity. Aging lymphocytes reconfigure transcriptional networks, undergo widespread organelle dysfunction, develop maladaptive stress responses, and redistribute into noncanonical tissue niches. Collectively, these alterations reduce antigen specificity and precision, promote innate-like immune behavior, and confer resistance to tolerance. These mechanisms result in concurrent immunodeficiency and autoimmunity, exemplified by two autoimmune diseases disproportionately affecting older adults: rheumatoid arthritis and giant cell arteritis.
    DOI:  https://doi.org/10.1172/JCI206227
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