bims-nimamd Biomed News
on Neuroimmunity and neuroinflammation in ageing and metabolic disease
Issue of 2025–07–13
25 papers selected by
Fawaz Alzaïd, Sorbonne Université
  1. A liver-centric help circuit revives CD8+ T cells via IL-27.
  2. Research is powered by technical talent - and recognition is finally on the rise.
  3. Giant map details nerves across a mouse's body: see stunning pics.
  4. Adipose tissue harbors pathogenic T cells in obesity that exacerbate inflammatory arthritis.
  5. Organelles share the load.
  6. High-coverage allele-resolved single-cell DNA methylation profiling reveals cell lineage, X-inactivation state, and replication dynamics.
  7. Mitochondrial control of macrophage polarity in tumors.
  8. Selective remodelling of the adipose niche in obesity and weight loss.
  9. Mrc1 (MMR, CD206) controls the blood proteome in reducing inflammation, age-associated organ dysfunction and mortality in sepsis.
  10. Replacing microglia to treat a brain disease.
  11. Spatial immunometabolic zonation in tuberculosis granulomas.
  12. Address Colombia's brain-health crisis.
  13. Antigen specificity shapes distinct aging trajectories of memory CD8⁺ T cells.
  14. Somatic mutations in TBX3 promote hepatic clonal expansion by accelerating VLDL secretion.
  15. EMP1 safeguards hematopoietic stem cells by suppressing sphingolipid metabolism and alleviating endoplasmic reticulum stress.
  16. Incretins and the cardiovascular system: bridging digestion with metabolism.
  17. NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis.
  18. CagriSema drives weight loss in rats by reducing energy intake and preserving energy expenditure.
  19. Caloric Restriction Promotes Resolution of Atherosclerosis in Obese Mice, while Weight Regain Accelerates its Progression.
  20. Lab drowning in paperwork? Hire an in-house writer.
  21. Bone marrow neutrophil density regulates myelopoiesis during obesity and weight loss.
  22. Weight loss alters adipose tissue beyond just reducing fat.
  23. Down-regulation of human-specific lncRNA TMEM9B-AS1 in skeletal muscle of people with type 2 diabetes affects ribosomal biogenesis.
  24. ICOS regulates IL-10 production in group 2 innate lymphoid cells via cholesterol and cortisol biosynthesis.
  25. Cell Marker Accordion: interpretable single-cell and spatial omics annotation in health and disease.
  1. Nat Immunol. 2025 Jul 08.
    A liver-centric help circuit revives CD8+ T cells via IL-27.
      
    DOI:  https://doi.org/10.1038/s41590-025-02204-9
  2. Nature. 2025 Jul 09.
    Research is powered by technical talent - and recognition is finally on the rise.
    Kelly Vere.
      
    Keywords:  Careers; Institutions; Lab life
    DOI:  https://doi.org/10.1038/d41586-025-01822-5
  3. Nature. 2025 Jul 10.
    Giant map details nerves across a mouse's body: see stunning pics.
    Mariana Lenharo.
      
    Keywords:  Cell biology; Imaging; Neuroscience
    DOI:  https://doi.org/10.1038/d41586-025-02156-y
  4. J Exp Med. 2025 Sep 01. pii: e20240677. [Epub ahead of print]222(9):
    Adipose tissue harbors pathogenic T cells in obesity that exacerbate inflammatory arthritis.
    Heather J Faust, Margaret H Chang, A Helena Jonsson, Erin Theisen, Nelson M LaMarche, William V Trim, Lydia Lynch, Peter A Nigrovic, Michael B Brenner.
      Obesity worsens inflammatory arthritis severity, even in non-load-bearing joints, but the mechanism is unknown. Here, we show that there is an immunological mechanism mediated by T cells in adipose tissue. Using an antigen-induced arthritis model with trackable, arthritis-inducing CD8+ OT-I T cells, we found that OT-I T cells home to visceral adipose tissue (VAT) and expand there in the obese high-fat diet (HFD) context. Transplant of VAT from arthritic mice increased arthritis severity in naïve recipient mice and was ameliorated by CD8 T cell depletion. Bulk RNA sequencing identified pro-inflammatory changes to OT-I T cells in VAT characterized by increased IFN α and γ signaling after HFD. Intraperitoneal injection of IFNα, but not IFNγ, expanded CD8 T cell numbers in VAT. HFD-induced expansion of VAT CD8 T cells was ameliorated with global Ifnar1 deletion, and importantly, genetic deletion of Ifnar1 in T cells decreased arthritis severity in obese mice. These results provide a mechanistic explanation of how obesity worsens autoimmunity.
    DOI:  https://doi.org/10.1084/jem.20240677
  5. Science. 2025 Jul 10. 389(6756): 130-131
    Organelles share the load.
    Marc Fransen.
      Peroxisome-mitochondria contact sites manage mitochondrial oxidative stress.
    DOI:  https://doi.org/10.1126/science.adz0109
  6. Nat Commun. 2025 Jul 08. 16(1): 6273
    High-coverage allele-resolved single-cell DNA methylation profiling reveals cell lineage, X-inactivation state, and replication dynamics.
    Nathan J Spix, Walid Abi Habib, Zhouwei Zhang, Emily Eugster, Hsiao-Yun Milliron, David Sokol, KwangHo Lee, Paula A Nolte, Jamie L Endicott, Kelly F Krzyzanowski, Toshinori Hinoue, Jacob Morrison, Benjamin K Johnson, Wanding Zhou, Hui Shen, Peter W Laird.
      DNA methylation patterns at crucial short sequence features, such as enhancers and promoters, may convey key information about cell lineage and state. The need for high-resolution single-cell DNA methylation profiling has therefore become increasingly apparent. Existing single-cell whole-genome bisulfite sequencing (scWGBS) studies have both methodological and analytical shortcomings. Inefficient library generation and low CpG coverage mostly preclude direct cell-to-cell comparisons and necessitate the use of cluster-based analyses, imputation of methylation states, or averaging of DNA methylation measurements across large genomic bins. Such summarization methods obscure the interpretation of methylation states at individual regulatory elements and limit our ability to discern important cell-to-cell differences. We report an improved scWGBS method, single-cell Deep and Efficient Epigenomic Profiling of methyl-C (scDEEP-mC), which offers efficient generation of high-coverage libraries. scDEEP-mC allows for cell type identification, genome-wide profiling of hemi-methylation, and allele-resolved analysis of X-inactivation epigenetics in single cells. Furthermore, we combine methylation and copy-number data from scDEEP-mC to identify single, actively replicating cells and profile DNA methylation maintenance dynamics during and after DNA replication. These analyses unlock further avenues for exploring DNA methylation regulation and dynamics and illustrate the power of high-complexity, highly efficient scWGBS library construction as facilitated by scDEEP-mC.
    DOI:  https://doi.org/10.1038/s41467-025-61589-1
  7. Immunity. 2025 Jul 08. pii: S1074-7613(25)00277-8. [Epub ahead of print]58(7): 1618-1620
    Mitochondrial control of macrophage polarity in tumors.
    Máté Kiss, Mikael J Pittet.
      Macrophages can foster pro- or anti-tumor immune environments. In this issue of Immunity, Clark et al. report that altering the composition of the mitochondrial electron transport chain reprograms macrophages toward a CXCL9hiSPP1lo immunostimulatory phenotype, thus amplifying anti-tumor immunity.
    DOI:  https://doi.org/10.1016/j.immuni.2025.06.008
  8. Nature. 2025 Jul 09.
    Selective remodelling of the adipose niche in obesity and weight loss.
    Antonio M A Miranda, Liam McAllan, Guianfranco Mazzei, Ivan Andrew, Iona Davies, Meryem Ertugrul, Julia Kenkre, Hiromi Kudo, Joana Carrelha, Bhavik Patel, Sophie Newton, Weihua Zhang, Alice Pollard, Amy Cross, Oliver McCallion, Mikyung Jang, Ka Lok Choi, Scarlett Brown, Yasmin Rasool, Marco Adamo, Mohamed Elkalaawy, Andrew Jenkinson, Borzoueh Mohammadi, Majid Hashemi, Robert Goldin, Laurence Game, Joanna Hester, Fadi Issa, Dylan G Ryan, Patricia Ortega, Ahmed R Ahmed, Rachel L Batterham, John C Chambers, Jaspal S Kooner, Damir Baranasic, Michela Noseda, Tricia Tan, William R Scott.
      Weight loss significantly improves metabolic and cardiovascular health in people with obesity1-3. The remodelling of adipose tissue (AT) is central to these varied and important clinical effects4. However, surprisingly little is known about the underlying mechanisms, presenting a barrier to treatment advances. Here we report a spatially resolved single-nucleus atlas (comprising 171,247 cells from 70 people) investigating the cell types, molecular events and regulatory factors that reshape human AT, and thus metabolic health, in obesity and therapeutic weight loss. We discover selective vulnerability to senescence in metabolic, precursor and vascular cells and reveal that senescence is potently reversed by weight loss. We define gene regulatory mechanisms and tissue signals that may drive a degenerative cycle of senescence, tissue injury and metabolic dysfunction. We find that weight loss reduces adipocyte hypertrophy and biomechanical constraint pathways, activating global metabolic flux and bioenergetic substrate cycles that may mediate systemic improvements in metabolic health. In the immune compartment, we demonstrate that weight loss represses obesity-induced macrophage infiltration but does not completely reverse activation, leaving these cells primed to trigger potential weight regain and worsen metabolic dysfunction. Throughout, we map cells to tissue niches to understand the collective determinants of tissue injury and recovery. Overall, our complementary single-nucleus and spatial datasets offer unprecedented insights into the basis of obese AT dysfunction and its reversal by weight loss and are a key resource for mechanistic and therapeutic exploration.
    DOI:  https://doi.org/10.1038/s41586-025-09233-2
  9. Nat Commun. 2025 Jul 07. 16(1): 6267
    Mrc1 (MMR, CD206) controls the blood proteome in reducing inflammation, age-associated organ dysfunction and mortality in sepsis.
    Damien Restagno, Mayank Saraswat, Peter V Aziz, Kathryn Smith, Amanda J Roberts, John Hintze, Jamey D Marth.
      Circulating blood proteins and enzymes are maintained within normal physiological and clinically relevant concentration ranges. Excursions from normality include diagnostic markers and causes of disease. Rapid and persistent changes in the levels and functions of circulating blood components can reflect the functions of multiple endocytic lectin receptors. The majority of non-albumin blood proteins are post-translationally modified with sialylated N-glycans bearing cryptic ligands of various endocytic lectin receptors. During time in circulation, these cryptic ligands are progressively unmasked thereby contributing to glycoprotein half-life and abundance. The relationships between distinct lectin receptors and their endogenous ligand repertoires are not easily established. Herein we apply a glycosidic linkage enrichment strategy to identify accumulating mannosylated plasma glycoproteins linked to the absence of the endocytic Mrc1 (MMR, CD206) mannose-binding lectin receptor. We find that Mrc1 controls the abundance of over two hundred circulating endogenous mannosylated proteins in healthy mice at steady state, including glycoproteins linked to inflammation, age-associated organ dysfunction, and elevated mortality in sepsis. Increased circulating Mrc1 levels previously ascribed to proteolysis during sepsis are proportional to mannosylated protein accumulation in the blood. Assignment of circulating mannosylated proteins to curated biological and pathogenic signaling pathways reveals significant overlap between Mrc1 dysfunction and human sepsis.
    DOI:  https://doi.org/10.1038/s41467-025-61346-4
  10. Science. 2025 Jul 10. 389(6756): 129-130
    Replacing microglia to treat a brain disease.
    Siling Du, Jonathan Kipnis.
      Swapping out the brain's immune cells can slow progression of a devastating neurological disease.
    DOI:  https://doi.org/10.1126/science.adz0113
  11. Nat Rev Immunol. 2025 Jul 07.
    Spatial immunometabolic zonation in tuberculosis granulomas.
    Amitava Sinha, Thomas Weichhart.
      
    DOI:  https://doi.org/10.1038/s41577-025-01210-0
  12. Nature. 2025 Jul;643(8071): 336
    Address Colombia's brain-health crisis.
    Juan F Cardona, Catalina Trujillo-Llano, Johnny Miller, Agustín Ibañez.
      
    Keywords:  Policy; Public health
    DOI:  https://doi.org/10.1038/d41586-025-02155-z
  13. Nat Commun. 2025 Jul 10. 16(1): 6394
    Antigen specificity shapes distinct aging trajectories of memory CD8⁺ T cells.
    Ines Sturmlechner, Abhinav Jain, Bin Hu, Rohit R Jadhav, Wenqiang Cao, Hirohisa Okuyama, Lu Tian, Cornelia M Weyand, Jörg J Goronzy.
      Memory T cells are a highly heterogeneous collection of antigen-experienced cells that undergo dynamic adaptations upon antigen re-encounter and environmental signals. This heterogeneity hinders studies on memory T cell durability and age-related dysfunction. Using chronic Epstein-Barr virus (EBV) infection and barcode-enabled antigen tracing, we assess the influence of age on memory states at the level of single antigen-specific CD8+ T cells. In young adults (<40 years), EBV-specific CD8+ T cells recognizing different antigenic peptides assume divergent preferred differentiation phenotypes. In older adults (>65-years), antigen-specific cells show largely distinct phenotypic and transcriptomic aging trajectories. Common to many albeit not all antigen-specific populations are maintained TCR diversity, gained natural killer cell-like, innate signatures and lost stem-like features while no evidence is seen for cellular senescence or exhaustion. TCR avidity contributes to these phenotypic differences and aging-related changes. Collectively, our data uncover divergent antigen-guided aging shifts in memory T cell phenotypes, which are informative for antigen selection in optimizing vaccine design and adoptive T cell therapy.
    DOI:  https://doi.org/10.1038/s41467-025-61627-y
  14. J Clin Invest. 2025 Jul 10. pii: e191855. [Epub ahead of print]
    Somatic mutations in TBX3 promote hepatic clonal expansion by accelerating VLDL secretion.
    Gregory Mannino, Gabriella Quinn, Min Zhu, Zixi Wang, Xun Wang, Boyuan Li, Meng-Hsiung Hsieh, Thomas Mathews, Lauren Zacharias, Wen Gu, Purva Gopal, Natalia Brzozowska, Peter Campbell, Matt Hoare, Glen Liszczak, Hao Zhu.
      Somatic mutations that increase clone fitness or resist disease are positively selected, but the impact of these mutations on organismal health remains unclear. We previously showed that Tbx3 deletion increases hepatocyte fitness within fatty livers. Here, we detected TBX3 somatic mutations in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). In mice, Tbx3 deletion protected against, whereas Tbx3 overexpression exacerbated MASLD. Tbx3 deletion reduced lipid overload by accelerating VLDL secretion. Choline deficient diets, which block VLDL secretion, abrogated this protective effect. TBX3 transcriptionally suppressed the conventional secretory pathway and cholesterol biosynthesis. Hdlbp is a direct target of TBX3 that is responsible for the altered VLDL secretion. In contrast to wild-type TBX3, the TBX3 I155S and A280S mutations found in patients failed to suppress VLDL secretion. In conclusion, TBX3 mutant clones expand during MASLD through increased lipid disposal, demonstrating that clonal fitness can benefit the liver at the cost of hyperlipidemia.
    Keywords:  Cell biology; Gastroenterology; Hepatitis
    DOI:  https://doi.org/10.1172/JCI191855
  15. Nat Commun. 2025 Jul 07. 16(1): 6247
    EMP1 safeguards hematopoietic stem cells by suppressing sphingolipid metabolism and alleviating endoplasmic reticulum stress.
    Lei Li, Yufei Lei, Yan Li, Yuxin Xie, Pusheng Hui, Xiaoyan Zang, Weiru Wu, Feng Wu, Jiankun Fan, Jianming Wang, Jieping Chen, Zhe Chen, Yu Hou.
      The long-term maintenance of hematopoietic stem cells (HSCs) relies on the regulation of endoplasmic reticulum (ER) stress at a low level, but the underlying mechanism remains poorly understood. Here, we demonstrate that suppression of ER stress improves the functions of HSCs and protects HSCs against ionizing radiation (IR)-induced injury. We identify epithelial membrane protein 1 (EMP1) as a key regulator that mitigates ER stress in HSCs. Emp1 deficiency leads to the accumulation of protein aggregates and elevated ER stress, ultimately resulting in impaired HSC maintenance and self-renewal. Mechanistically, EMP1 is located within the ER and interacts with ceramide synthase 2 (CERS2) to limit the production of a class of sphingolipids, dihydroceramides (dhCers). DhCers accumulate in Emp1-deficient HSCs and induce protein aggregation. Furthermore, Emp1 deficiency renders HSCs more susceptible to IR, while overexpression of Emp1 or inhibition of CERS2 protects HSCs against IR-induced injury. These findings highlight the critical role played by the EMP1-CERS2-dhCers axis in constraining ER stress and preserving HSC potential.
    DOI:  https://doi.org/10.1038/s41467-025-61552-0
  16. Lancet Diabetes Endocrinol. 2025 Jul 07. pii: S2213-8587(25)00166-4. [Epub ahead of print]
    Incretins and the cardiovascular system: bridging digestion with metabolism.
    Angelo Avogaro, Gian Paolo Fadini.
      The mechanisms driving the cardiovascular and renal benefits of therapies targeting intestinal hormones in type 2 diabetes are still not fully understood. We propose that incretin hormones-glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)-act as a critical link connecting digestion, metabolism, and cardiovascular function, supporting physiological adaptations to nutrient intake. Incretin hormones help regulate blood flow and cardiac activity, enhancing nutrient absorption while protecting the heart and vessels. After meals, incretin hormones promote vasodilation-especially in the splanchnic and peripheral circulations-via nitric oxide, improving endothelial function, vascular flexibility, and blood pressure control, which supports tissue perfusion and meets the body's increased metabolic demands. GLP-1 also has mild inotropic effects, promoting efficient circulation without straining the heart. At the same time, vasodilation boosts glucose and lipid uptake, linking digestion directly to energy metabolism. These mechanisms lower vascular resistance, reduce cardiac workload, and improve myocardial glucose use, which becomes especially valuable during ischaemic events. Incretins also have anti-inflammatory and antioxidant effects, which help prevent endothelial dysfunction and arterial stiffening, reducing the risk of atherosclerosis. Clinically, GLP-1 receptor agonists and dual GLP-1 and GIP receptor agonists leverage these effects to improve cardiovascular and possibly renal outcomes in people with type 2 diabetes or obesity. By linking digestion, metabolism, and cardiovascular health, incretin-based therapies do more than just regulate blood sugar; they help reduce morbidity and mortality and are becoming a core component of modern diabetes care.
    DOI:  https://doi.org/10.1016/S2213-8587(25)00166-4
  17. Nat Commun. 2025 Jul 07. 16(1): 6254
    NXT2 is a key component of the RNA nuclear export factor complex in the human testis and essential for spermatogenesis.
    Ann-Kristin Dicke, Ammar Ahmedani, Lin Ma, Leonie Herrmann, Godfried W van der Heijden, Sophie A Koser, Claudia Krallmann, Oguzhan Kalyon, Miguel J Xavier, Joris A Veltman, Sabine Kliesch, Nina Neuhaus, Noora Kotaja, Frank Tüttelmann, Birgit Stallmeyer.
      In eukaryotes, the nucleocytoplasmic export of bulk poly(A)+-mRNAs through the nuclear pore complex is mediated by the ubiquitously expressed NXT1-NXF1 heterodimer. In humans, NXT1 has an X-chromosomal paralog, NXT2, which exhibits testis-enriched expression, suggesting a role in spermatogenesis. Here, we report the in vivo interaction of NXT2 with crucial components of the nuclear export machinery, including NXF1, the testis-specific NXF1 paralogs NXF2 and NXF3, and nuclear pore complex proteins. Binding to NXF2 and NXF3 is mediated by the NTF2-like domain of NXT2. By identifying infertile men with loss-of-function variants in NXT2 and NXF3, we link the impaired NXT2-NXF activity to disturbed germ cell development. The predominant absence of germ cells in men with NXT2 deficiency indicates its critical function already during fetal or first steps of germ cell development. In contrast, loss of NXF3 affects later stages of spermatogenesis, resulting in quantitatively and qualitatively impaired sperm production.
    DOI:  https://doi.org/10.1038/s41467-025-61463-0
  18. Nat Metab. 2025 Jul 08.
    CagriSema drives weight loss in rats by reducing energy intake and preserving energy expenditure.
    Julie Mie Jacobsen, Jens Frey Halling, Ida Blom, Jaime Moreno Martinez, Bjørn Hald, Kent Pedersen, Johannes Josef Fels, Søren Snitker, Anna Secher, Sofia Lundh, Carel W le Roux, Kirsten Raun, Marc L Reitman, Rune Ehrenreich Kuhre.
      CagriSema is a combination of amylin (cagrilintide) and glucagon-like peptide-1 (semaglutide) analogues being developed for weight management. Here, we show that CagriSema blunts metabolic adaptation in rats. Quantifying CagriSema's action on energy intake and expenditure in rats we observe 12% weight loss with a 39% reduction in food intake. By contrast, pair-feeding causes less-pronounced weight loss, while weight matching requires a 51% decrease in food intake. Therefore, approximately one-third of CagriSema's weight loss efficacy arises from an effect on energy expenditure, the blunting of metabolic adaptation, which contributes to the successful treatment of obesity.
    DOI:  https://doi.org/10.1038/s42255-025-01324-8
  19. J Clin Invest. 2025 Jul 08. pii: e172198. [Epub ahead of print]
    Caloric Restriction Promotes Resolution of Atherosclerosis in Obese Mice, while Weight Regain Accelerates its Progression.
    Bianca Scolaro, Franziska Krautter, Emily J Brown, Aleepta Guha Ray, Rotem Kalev-Altman, Marie Petitjean, Sofie Delbare, Casey Donahoe, Stephanie Pena, Michela L Garabedian, Cyrus A Nikain, Maria Laskou, Ozlem Tufanli, Carmen Hannemann, Myriam Aouadi, Ada Weinstock, Edward A Fisher.
      While weight loss is highly recommended for those with obesity, >60% will regain their lost weight. This weight cycling is associated with elevated risk of cardiovascular disease, relative to never having lost weight. How weight loss/regain directly influence atherosclerotic inflammation is unknown. Thus, we studied short-term caloric restriction (stCR) in obese hypercholesterolemic mice, without confounding effects from changes in diet composition. Weight loss was found to promote atherosclerosis resolution independent of plasma cholesterol. From single-cell RNA-sequencing and subsequent mechanistic studies, this can be partly attributed to a unique subset of macrophages accumulating with stCR in epididymal white adipose tissue (eWAT) and atherosclerotic plaques. These macrophages, distinguished by high expression of Fcgr4, help to clear necrotic cores in atherosclerotic plaques. Conversely, weight regain (WR) following stCR accelerated atherosclerosis progression with disappearance of Fcgr4+ macrophages from eWAT and plaques. Furthermore, WR caused reprogramming of immune progenitors, sustaining hyper-inflammatory responsiveness. In summary, we have developed a model to investigate the inflammatory effects of weight cycling on atherosclerosis and the interplay between adipose tissue, bone marrow, and plaques. The findings suggest potential approaches to promote atherosclerosis resolution in obesity and weight cycling through induction of Fcgr4+ macrophages and inhibition of immune progenitor reprogramming.
    Keywords:  Adipose tissue; Atherosclerosis; Cardiology; Inflammation; Innate immunity; Metabolism
    DOI:  https://doi.org/10.1172/JCI172198
  20. Nature. 2025 Jul 09.
    Lab drowning in paperwork? Hire an in-house writer.
    Béla Z Schmidt.
      
    Keywords:  Careers; Funding; Lab life; Publishing
    DOI:  https://doi.org/10.1038/d41586-025-01823-4
  21. J Exp Med. 2025 Sep 01. pii: e20242174. [Epub ahead of print]222(9):
    Bone marrow neutrophil density regulates myelopoiesis during obesity and weight loss.
    Quin T Waterbury, Jin Qian, Hualong Zheng, Amanda Dirnberger, Oakley C Olson, Ruth A White, Feijing Wu, Hiroki Kobayashi, Ermanno Malagola, Yosuke Ochiai, Ruhong Tu, Biyun Zheng, Adama Diaby, Harry Nagendra, Jonathan S LaBella, Leah Zamechek, Judith Korner, Ana B Emiliano, Anthony W Ferrante, Emmanuelle Passegué, Timothy C Wang.
      The bone marrow (BM) is altered in obesity to promote myeloid cell generation, but the mechanisms driving these changes remain unclear. Here, we show that obesogenic stimuli promote adipose tissue macrophages to recruit neutrophils from the BM in mice. Recruitment of BM neutrophils activates hematopoietic stem cells, which produce myeloid cells that accumulate in the circulation and drive inflammation. This recruitment is not resolved by weight loss, leading to sustained myelopoiesis in previously obese mice. Inhibiting neutrophil recruitment out of the BM in obese mice or during weight loss reduces BM myelopoiesis and adipose tissue inflammation, and improves glucose tolerance. In humans with obesity, plasma neutrophil chemokines are increased, correlate with increased insulin resistance, but do not decrease with weight loss. Our results demonstrate that neutrophil recruitment is a key mediator of myelopoiesis during obesity, and targeting this pathway is a potential strategy to improve inflammation during obesity and weight loss.
    DOI:  https://doi.org/10.1084/jem.20242174
  22. Nature. 2025 Jul 09.
    Weight loss alters adipose tissue beyond just reducing fat.
    Evan D Rosen, Margo P Emont.
      
    Keywords:  Metabolism; Obesity; Transcriptomics
    DOI:  https://doi.org/10.1038/d41586-025-02056-1
  23. Sci Adv. 2025 Jul 11. 11(28): eads4371
    Down-regulation of human-specific lncRNA TMEM9B-AS1 in skeletal muscle of people with type 2 diabetes affects ribosomal biogenesis.
    Ilke Sen, Jonathon A B Smith, Elena Caria, Iurii Orlov, Mladen Savikj, Aidan J Brady, Kristian Lian, Stian Ellefsen, Juleen R Zierath, Anna Krook.
      Long noncoding RNAs (lncRNAs) are important regulators of skeletal muscle physiology, with altered expression noted in several human diseases including type 2 diabetes. We report that TMEM9B-AS1, a previously uncharacterized lncRNA, is down-regulated in skeletal muscle of men with type 2 diabetes and skeletal muscle from individuals with sarcopenia. Silencing of TMEM9B-AS1 in primary human myotubes attenuated protein synthesis, concomitant with reduced phosphorylation of ribosomal protein S6. Moreover, we show that TMEM9B-AS1 plays a pivotal role in regulation of ribosomal biogenesis by facilitating messenger RNA stabilization of the transcription factor MYC through direct physical interaction with the RNA binding protein, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1). Disrupted ribosomal biogenesis resulting from TMEM9B-AS1 silencing leads to decreased expression of muscle contractile and structural proteins important for maintenance of skeletal muscle mass and function. Collectively, our data reveal a role of TMEM9B-AS1 in skeletal muscle loss associated with metabolic disorders.
    DOI:  https://doi.org/10.1126/sciadv.ads4371
  24. J Clin Invest. 2025 Jul 08. pii: e193134. [Epub ahead of print]
    ICOS regulates IL-10 production in group 2 innate lymphoid cells via cholesterol and cortisol biosynthesis.
    Yoshihiro Sakano, Kei Sakano, Benjamin P Hurrell, Mohammad H Kazemi, Xin Li, Stephen Shen, Omid Akbari.
      Group 2 innate lymphoid cells (ILC2s) play a crucial role in inducing type 2 inflammation in the lungs in response to allergens. Our study investigated the regulatory mechanism of IL-10 production by ILC2s and its impact on airway hyperreactivity (AHR), focusing on the role of ICOS. We found that inhibiting ICOS in pulmonary ILC2s significantly enhances IL-10 production. The absence of ICOS reprograms ILC2 steroid metabolism, leading to increased cholesterol and cortisol biosynthesis, and subsequent Glucocorticoid receptor (GR) activation. This reprogramming regulates MAF and NFIL3 activation, promoting IL-10 production. Notably, in vivo GR inhibition or ILC2-specific GR deficiency exacerbated AHR development in multiple mouse models. We extended these findings to human ILC2s, demonstrating concordant results between murine models and human cells. Our results indicate that ICOS negatively regulates IL-10 production in ILC2s by controlling cholesterol and cortisol biosynthesis. This mechanism provides new insights into the complex interplay between ILC2s, ICOS, and glucocorticoid signaling in the context of allergic airway inflammation.
    Keywords:  Allergy; Asthma; Cholesterol; Immunology; Pulmonology
    DOI:  https://doi.org/10.1172/JCI193134
  25. Nat Commun. 2025 Jul 07. 16(1): 5399
    Cell Marker Accordion: interpretable single-cell and spatial omics annotation in health and disease.
    Emma Busarello, Giulia Biancon, Ilaria Cimignolo, Fabio Lauria, Zuhairia Ibnat, Christian Ramirez, Gabriele Tomè, Marianna Ciuffreda, Giorgia Bucciarelli, Alessandro Pilli, Stefano Maria Marino, Vittorio Bontempi, Federica Ress, Kristin R Aass, Jennifer VanOudenhove, Luca Tiberi, Maria Caterina Mione, Therese Standal, Paolo Macchi, Gabriella Viero, Stephanie Halene, Toma Tebaldi.
      Single-cell technologies offer a unique opportunity to explore cellular heterogeneity in health and disease. However, reliable identification of cell types and states represents a bottleneck. Available databases and analysis tools employ dissimilar markers, leading to inconsistent annotations and poor interpretability. Furthermore, current tools focus mostly on physiological cell types, limiting their applicability to disease. We present the Cell Marker Accordion, a user-friendly platform providing automatic annotation and unmatched biological interpretation of single-cell populations, based on consistency weighted markers. We validate our approach on multiple single-cell and spatial datasets from different human and murine tissues, improving annotation accuracy in all cases. Moreover, we show that the Cell Marker Accordion can identify disease-critical cells and pathological processes, extracting potential biomarkers in a wide variety of disease contexts. The breadth of these applications elevates the Cell Marker Accordion as a fast, flexible, faithful and standardized tool to annotate and interpret single-cell and spatial populations in studying physiology and disease.
    DOI:  https://doi.org/10.1038/s41467-025-60900-4
This page is being maintained by Thomas Krichel. It was last updated on 2025‒07‒13 at 15:26.