Immunology

Within the IL-12 superfamily of heterodimeric cytokines, IL-12 and IL-23, which share a subunit, are among the most pro-inflammatory members. Both are primarily produced by phagocytes and have key roles in activating and regulating T lymphocytes, natural killer cells and innate lymphoid cells. IL-12 predominantly promotes type 1 immune responses, whereas IL-23 is closely associated with type 3 immunity. Their receptors are also heterodimeric and, upon engagement, they trigger ‘cytokine polarization’ (the imprinting of functional identities on immune cells by activating lineage-defining transcription factors), which contributes to inflammation and immunopathology. IL-12 has a key role in various inflammatory conditions and is a potent driver of antitumour immunity, and IL-12 delivery is being explored in several clinical trials in cancer. By contrast, IL-23 is essential for maintaining barrier tissue integrity, yet its dysregulation is a central driver of autoimmune diseases such as psoriasis. Beyond their well-established pro-inflammatory roles, studies of both cytokines have also yielded paradoxical findings. Emerging evidence suggests that both IL-12 and IL-23 can also attenuate immune responses. In this Review, we explore the discovery of IL-12 and IL-23, their canonical pro-inflammatory functions, and recent insights into their immunoregulatory roles in inflammation, cancer and autoimmunity. Here, Becher and colleagues examine the paradoxical roles of IL-12 and IL-23, two IL-12 family cytokines that drive type 1 and type 3 immune responses, respectively. Both promote inflammation by activating T cells, natural cells and innate lymphoid cells through cytokine polarization, yet IL-12 also supports antitumour immunity and IL-23 maintains barrier integrity. This Review highlights emerging evidence that both cytokines can also dampen immune responses, revealing unexpected regulatory roles in cancer, autoimmunity and tissue homeostasis.

Platelets are cell fragments that plug leaks in blood vessels, preventing bleeding. However, they also form clots that impede blood flow (thrombosis) and increase inflammation.

Activated platelets, which can bind to each other, and hyporesponsive platelets, which do not form clots, are detected in patients with acute severe infections, such as COVID-19 and sepsis. How to uncouple the protective and harmful proinflammatory functions of platelets is a therapeutic dilemma.

In Science, researchers report the formation of platelet-derived integrin-and tetraspanin-enriched tethers (PITTs) in patients with severe infections.

PITTs, which are enriched in specific platelet proteins, remain anchored to the blood vessel wall (endothelium) and promote neutrophil recruitment, inflammation, and tissue damage, whereas the main platelet body shears off and reenters circulation in a hyporesponsive state. PITTs may contribute to blood clotting, immune dysregulation, and bleeding complications that characterize severe infections.

Learn more in a new #SciencePerspective: https://scim.ag/4pYNOyA

The immune system has evolved intricate and sophisticated mechanisms to recognize and eliminate tumours. Among these, T helper 17 (TH17) cells seem to have a complex role in tumour immunity. Substantial evidence indicates that TH17 cells can impair the ability of immune cells to kill tumours, but growing research suggests that TH17 cells may also be crucial for facilitating effective antitumour immune responses. This apparent paradox is likely rooted, at least in part, in the remarkable plasticity of TH17 cells, which can adopt a range of effector functions depending on the environmental cues present in distinct tissue niches. Understanding the spectrum of functional adaptations that TH17 cells can undergo is especially important in cancer, where tumours exhibit substantial tissue heterogeneity. Here, we examine the context-dependent roles of TH17 cells in cancer, with a focus on the environmental signals and regulatory networks that may shape their phenotypes during cancer development and progression. Finally, we discuss how these insights could inform strategies to manipulate TH17 cells for the development of next-generation cancer immunotherapies. T helper 17 (TH17) cells can have both pro-tumour and antitumour effects. Understanding how they are regulated by environmental and regulatory cues according to context will inform strategies to harness their activity for the development of next-generation cancer immunotherapies.

Foundations of the Human Immune System
Immunity is defined as the body’s ability to resist infection through specialized cells and molecules.
Types of Immunity:
Innate (Natural) Immunity:
This is the first line of defense. It is non-specific, meaning it reacts the same way to all pathogens. It does not require prior exposure and does not have "memory."
• External Defenses: The first line of defense includes physical, chemical, and biological barriers. The skin serves as a structural barrier, while secretions like lactic acid in sweat and hydrochloric acid in the stomach maintain acidic environments to halt microbial growth.
• Pattern Recognition: Phagocytic cells like macrophages and dendritic cells identify unique microbial substances called pathogen-associated molecular patterns (PAMPs) using pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs).
• Phagocytosis: Once a pathogen is recognized, specialized white blood cells (neutrophils, monocytes, and macrophages) engulf and destroy the particle. This process involves seven steps, including physical contact, the formation of a phagosome, and the fusion of lysosomal granules to create a phagolysosome where digestion occurs.
• The Oxidative Burst: To kill ingested microbes, phagocytes increase oxygen consumption to generate toxic oxygen radicals, such as superoxide and hydrogen peroxide.
• Natural Killer (NK) Cells: These cells represent the first line of defense against virally infected and tumor cells. They function through a balance of inhibitory signals (recognizing MHC class I molecules) and activating signals. If activated, they release perforins and granzymes to induce apoptosis in the target cell.
• Adaptive (Acquired) Immunity:
Adaptive immunity is characterized by specificity for individual pathogens and the ability to remember prior exposures (immunologic memory).
• Antigen Presentation (MHC): For T cells to recognize an antigen, it must be "presented" by Major Histocompatibility Complex (MHC) molecules. MHC Class I molecules present endogenous antigens (produced inside the cell, like viruses) to CD8+ cytotoxic T cells. MHC Class II molecules present exogenous antigens (taken in from outside) to CD4+ helper T cells.
• T-Cell Effector Actions:
    ◦ Helper T (Th) cells produce cytokines that orchestrate the activity of other cells, such as B cells and macrophages.
    ◦ Cytotoxic T (Tc) cells directly kill infected or malignant cells by releasing cytotoxic granules or ligating death receptors.
• B-Cell and Antibody Responses: B cells differentiate into plasma cells to secrete antibodies.
    ◦ T-dependent antigens require help from T cells to stimulate B-cell proliferation and isotype switching (e.g., from IgM to IgG).
    ◦ Antibody functions include opsonization (coating pathogens to enhance phagocytosis), neutralization of toxins, and antibody-dependent cellular cytotoxicity (ADCC).

Infant immunity is not just passively transferred from the mother—it's built from scratch. FAB clonal profiling reveals newborns rapidly forge their own antibody repertoires, rewriting the textbook on early-life immune development.

Which begs the question, how quickly do newborns begin building their own antibody defenses? In our new multi-center study with colleagues from Utrecht, Shenzhen, Beijing, and Wuhan, we show that infants start generating unique IgA1 and IgG1 antibody repertoires within 7–11 weeks after birth, distinct from maternal serum and breast milk.

What we found: By 7-11 weeks after birth (T2), infant IgA1 clones in serum are new and do not overlap with maternal milk or serum, indicating they are produced by the infant. Infant IgG1 repertoires at T2 contain many “new” clones, while maternal IgG1 signatures faded as expected—strong evidence that newborns begin producing IgG1 antibodies early on. From this small cohort, we found no convincing evidence of milk maternal antibody transfer into infant circulation, prompting a re-examination of some long-held assumptions.

How we did it: We used intact LC–MS–based FAB clonal profiling to resolve antibody repertoires with clonal precision across maternal serum, maternal milk, and infant serum. This approach quantitatively tracks overlapping versus unique clones, pinpointing the emergence of infant-origin antibodies.

Why it matters: These findings shift our understanding of early-life humoral immunity—from how maternal antibodies shape neonatal responses, to when and how we time early-life vaccinations for durable protection. This method also opens a path to study neonatal vaccine responses and maternal–infant immune interactions with unprecedented resolution.

To read the full publication follow this link: https://lnkd.in/eu7xfaiR

Grateful to work with this outstanding international team: Albert Bondt, Minjie Tan, Danique van Rijswijck, Yuexiao Chen, Shuai Zhu, Ye Tian Tianhui Lin, Yuanzhen Zhang, Yanyi Huang, Guanbo Wang, Jing Zhu, Juanjuan Guo, Albert Heck

#UtrechtUniversity #BeijingAcademyOfScienceAndTechnology #ZhongnanHospitalOfWuhanUniversity #PekingUniversityBeijing

#InfantImmunity #IgA1 #IgG1 #AntibodyRepertoires #MassSpectrometry #ClonalProfiling #Proteomics #Neonatology #Vaccines | 10 comments on LinkedIn

I love how this newly discovered immune signaling in plants looks kind of like fireworks. It's a celebration of botany! That and more of the best from Science Magazine and science in this edition of #ScienceAdviser: https://lnkd.in/gaedvdfa

Deuxième poster de la série NK !
Ce poster explore le développement des cellules Natural Killer, depuis leur origine jusqu’à leur activation.
Les cellules Natural Killer sont des cellules de l’immunité innée dont le développement s’inscrit dans la lignée lymphoïde. Elles se développent principalement dans la moelle osseuse, à partir des cellules souches hématopoïétiques (CSH), via le progéniteur lymphoïde commun (CLP). Ce progéniteur est également à l’origine des lymphocytes B et T, ainsi que des cellules lymphoïdes innées, incluant les cellules NK.

#Immunologie #CellulesNK #Biologie #RechercheScientifique #VulgarisationScientifique

Long COVID (LC) involves a spectrum of chronic symptoms after acute severe acute respiratory syndrome coronavirus 2 infection. Current hypotheses for the pathogenesis of LC include persistent virus, tissue damage, autoimmunity, endocrine insufficiency, immune dysfunction and complement activation. We performed immunological, virological, transcriptomic and proteomic analyses from a cohort of 142 individuals between 2020 and 2021, including uninfected controls (n = 35), acutely infected individuals (n = 54), convalescent controls (n = 24) and patients with LC (n = 28). The LC group was characterized by persistent immune activation and proinflammatory responses for more than 180 days after initial infection compared with convalescent controls, including upregulation of JAK-STAT, interleukin-6, complement, metabolism and T cell exhaustion pathways. Similar findings were observed in a second cohort enrolled between 2023 and 2024, including convalescent controls (n = 20) and patients with LC (n = 18). These data suggest that LC is characterized by persistent activation of chronic inflammatory pathways, suggesting new therapeutic targets and potential biomarkers of disease. Long COVID (LC) involves a spectrum of chronic symptoms after resolution of acute severe acute respiratory syndrome coronavirus 2 infection. Barouch and colleagues show that LC is characterized by persistent activation of chronic inflammatory pathways and T cell exhaustion.

Every leukocyte class shall have its day in atherosclerosis. With an international team we summarize the current evidence supporting mechanisms by which mast cells can participate in this disease. Inflammation has many faces, and reaginic antibody (IgEs) can link adaptive to innate immunity unleashing a multitude of mast cell mediators that can modulate arterial and microvascular biology. #atherosclerosis #angiogenesis #inflammation #allergy #cardiology #cardiovascularmedicine #heartattack #myocardialinfarction #immunology #microvasculature

Since the discovery of the segmented shape of the neutrophil nucleus, scientists have pondered its physiological relevance. Yet, to this day, neither the functional relevance nor the molecular mechanisms underlying the segmentation of the neutrophil nucleus are fully understood. Some experimental evidence supports a role of nuclear segmentation in efficient neutrophil migration but its impact on key neutrophil functions, such as phagocytosis, degranulation or production of reactive oxygen species, remains unclear. Nonetheless, the role of nuclear shape in remodelling chromatin and regulating gene expression has high potential for biological and translational relevance. This Review aims to compile and connect the current studies on the neutrophil nucleus, while also discussing studies in other cell types that could inform us about the relevance or mechanisms of nuclear segmentation. In this Review, the authors consider a long-standing immunological conundrum — why do neutrophils have a segmented nucleus? They discuss the mechanisms that may underlie segmentation of the neutrophil nucleus and explain how nuclear segmentation may affect neutrophil functions, including migration and phagocytosis.

The process of phagocytosis creates intracellular compartments (organelles known as phagosomes) that are central hubs for innate immune sensing of potentially dangerous microorganisms, cells, cellular debris and foreign objects. Receptors, enzymes and signalling molecules are specifically enriched in these compartments, wherein they learn everything they can about the phagocytosed material and signal for the cell to mount appropriate responses. The phagosome organelle is also a compartment that facilitates nutrient and metabolite harvesting from internalized materials. This Review explores recent developments in our understanding of phagocytosis as a specific mechanism of innate immune sensing. We discuss efforts to identify the catalogue of proteins that are enriched in different types of phagosomes to learn how these molecules work together to tailor inflammatory and antimicrobial immune responses. In this Review, Li and Underhill discuss recent advances in understanding the process of phagocytosis. The authors highlight how phagocytosis is integral for innate immune sensing and explain how the phagocytosed material itself shapes the phagocytosis process.

🚀 New preprint: A single-cell cytokine dictionary of human peripheral blood

Excited to share our new preprint, “A single-cell cytokine dictionary of human peripheral blood”.

In this work, we generated the Human Cytokine Dictionary:
👉 9.7 million single-cell transcriptomes across
👉 12 human PBMC donors and
👉 90 individual cytokine stimulations,
👉 by far the largest single-cell perturbation dataset from primary human immune cells to date.

This dataset lets us systematically map how human immune cell types respond to cytokines, uncover cell type–specific activities, donor-specific vs consensus responses, cytokine similarity groups, and higher-order cytokine-cytokine and cell-cell communication networks. A particularly interesting story is the IL-32-β–initiated cascade that rewires myeloid programs from antiviral/Th1-type responses towards a neutrophil-driven, IL-10–modulated inflammatory state.

To make this resource broadly usable, we also introduce huCIRA (Human Cytokine Immune Response Analysis), a Python package that
• exposes cytokine-induced gene and program signatures, and
• allows researchers to decode cytokine activity in their own single-cell and spatial transcriptomic datasets.
We showcase this on datasets from systemic lupus erythematosus, multiple sclerosis, and NSCLC.

Huge congratulations and thanks to our four co–first authors Lukas Oesinghaus, Sören Becker, Larsen Vornholz and Efi Papalexi,👏 for driving this enormous effort.

This project was only possible thanks to a fantastic collaboration with Parse Biosciences, leveraging their GigaLab platform to reach this unprecedented data scale, and to the Seelig lab for a truly inspiring and fun partnership across engineering, computation, and immunology.

I also want to thank Nir Hacohen and colleagues for their pioneering mouse Immune Dictionary (Cui et al., Nature 2024), which provided a key conceptual and analytical reference point for our human cytokine dictionary.

You can read the preprint here:
🔗 https://lnkd.in/gFB3NAdC

Looking ahead, I hope this work can serve as a blueprint for analyzing the many large-scale perturbation datasets to come - as both a biological reference and a testbed for virtual cell models of cytokine biology.
🔧 Code & huCIRA package: https://lnkd.in/g7cMPic3
🧰 For broader single-cell perturbation analysis, also check out pertpy in the scverse ecosystem: https://lnkd.in/g_7cpUfH

Looking forward to feedback, reuse of the Human Cytokine Dictionary and huCIRA by the community. | 13 comments on LinkedIn

Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system with essential roles in immune surveillance, tissue homeostasis and inflammation. In the kidney, NK cells comprise a heterogeneous population that includes both circulating and tissue-resident subsets, each shaped by environmental cues and genetic factors through interactions with major histocompatibility complex class I molecules. The latest research data highlight multifaceted NK cell contributions to kidney physiology and pathology. In steady state, NK cells support kidney immune surveillance and crosstalk with epithelial, myeloid and lymphoid cells. In disease, NK cells can promote injury through direct cytotoxicity and pro-inflammatory cytokine release. Experimental models demonstrate pathogenic roles for NK cells in ischaemia–reperfusion injury and chronic kidney disease, with emerging evidence implicating NK cell-derived mediators in fibrogenesis. In kidney transplantation, NK cells are effectors of antibody-dependent and antibody-independent allograft injury. Educated NK cells expressing CD16a (also known as FcγRIIIa) mediate antibody-dependent cellular cytotoxicity, whereas loss of inhibitory receptor–ligand interactions (for example, due to killer immunoglobulin-like receptor–HLA mismatch) can trigger NK cell activation independently of donor-specific antibodies. Advances in high-resolution profiling have deepened mechanistic insights and uncovered novel therapeutic targets. Here, we provide a comprehensive overview of NK cell biology in the kidney, highlighting roles in health, disease and transplantation, and we consider its translational implications for diagnosis and therapy. This Review discusses the latest advances in natural killer cell biology, including insights into population heterogeneity, and examines the roles of these innate lymphocytes in kidney health and disease, as well as their contribution to kidney allograft rejection and its therapeutic implications.

🟥 Bringing the Human Immune System into Mice: The Latest Breakthroughs in Humanized Mouse Models

Scientists have long faced a challenge in studying the human immune system: many immune responses cannot be accurately replicated in ordinary experimental animals. To address this problem, humanized mouse models have emerged and have made significant progress in recent years, gradually becoming a "key bridge" in immunology and translational medicine.

A humanized mouse refers to a mouse in which a functional human immune system is reconstructed through genetic engineering and cell transplantation techniques in an immunodeficient mouse. Early models primarily relied on injecting human peripheral blood immune cells or hematopoietic stem cells. While this could temporarily create human immune cells, it suffered from limitations such as incomplete immune composition and poor stability. In recent years, a new generation of humanized models has significantly improved the development and functional maturity of human T cells, B cells, and innate immune cells by optimizing the immunodeficient background, introducing human cytokine genes, and combining the transplantation of human hematopoietic stem cells with tissues (such as the thymus and liver).

These improvements have enabled humanized mice to demonstrate unique value in several fields. In tumor immunology research, they can be used to evaluate the efficacy and safety of therapies such as immune checkpoint inhibitors and CAR-T cells; in infection and vaccine research, the models can more accurately simulate the human immune response process; and in autoimmune disease and transplant rejection research, humanized mice also provide an important platform for mechanism analysis and drug screening.

Of course, these models still face challenges, such as high construction costs and differences between the human immune system and the mouse microenvironment. However, with the development of gene editing, stem cell, and microenvironment engineering technologies, humanized mice are constantly evolving towards being "closer to humans." It is foreseeable that they will play an increasingly central role in the development of precision medicine and novel immunotherapies. Follow us (www.csteamus.com) to learn more about the biological model products and related services provided by CSTEAM biotechnology.

Keywords:
Humanized mice, immune system reconstruction, tumor immunology, hematopoietic stem cells, translational medicine

The Chinese Immune Multi-Omics Atlas

🧠 𝗔 𝗽𝗮𝗽𝗲𝗿 𝗮 𝗱𝗮𝘆 𝗸𝗲𝗲𝗽𝘀 𝗯𝗿𝗮𝗶𝗻 𝗱𝗲𝗰𝗮𝘆 𝗮𝘄𝗮𝘆 🧠
Wednesday, 14 January 2026

𝘛𝘩𝘪𝘴 𝘴𝘵𝘶𝘥𝘺 𝘱𝘳𝘦𝘴𝘦𝘯𝘵𝘴 𝘊𝘐𝘔𝘈 (𝘊𝘩𝘪𝘯𝘦𝘴𝘦 𝘐𝘮𝘮𝘶𝘯𝘦 𝘔𝘶𝘭𝘵𝘪-𝘖𝘮𝘪𝘤𝘴 𝘈𝘵𝘭𝘢𝘴), 𝘪𝘯𝘵𝘦𝘨𝘳𝘢𝘵𝘪𝘯𝘨 𝘱𝘰𝘱𝘶𝘭𝘢𝘵𝘪𝘰𝘯-𝘴𝘤𝘢𝘭𝘦 𝘴𝘪𝘯𝘨𝘭𝘦-𝘤𝘦𝘭𝘭 𝘵𝘳𝘢𝘯𝘴𝘤𝘳𝘪𝘱𝘵𝘰𝘮𝘪𝘤𝘴, 𝘤𝘩𝘳𝘰𝘮𝘢𝘵𝘪𝘯 𝘢𝘤𝘤𝘦𝘴𝘴𝘪𝘣𝘪𝘭𝘪𝘵𝘺, 𝘢𝘯𝘥 𝘨𝘦𝘯𝘦𝘵𝘪𝘤𝘴 𝘵𝘰 𝘭𝘪𝘯𝘬 𝘯𝘰𝘯𝘤𝘰𝘥𝘪𝘯𝘨 𝘥𝘪𝘴𝘦𝘢𝘴𝘦 𝘷𝘢𝘳𝘪𝘢𝘯𝘵𝘴 𝘵𝘰 𝘪𝘮𝘮𝘶𝘯𝘦 𝘤𝘦𝘭𝘭 𝘴𝘵𝘢𝘵𝘦𝘴, 𝘳𝘦𝘨𝘶𝘭𝘢𝘵𝘰𝘳𝘺 𝘦𝘭𝘦𝘮𝘦𝘯𝘵𝘴, 𝘢𝘯𝘥 𝘨𝘦𝘯𝘦 𝘯𝘦𝘵𝘸𝘰𝘳𝘬𝘴, 𝘸𝘩𝘪𝘭𝘦 𝘳𝘦𝘷𝘦𝘢𝘭𝘪𝘯𝘨 𝘴𝘦𝘹- 𝘢𝘯𝘥 𝘢𝘯𝘤𝘦𝘴𝘵𝘳𝘺-𝘥𝘦𝘱𝘦𝘯𝘥𝘦𝘯𝘵 𝘪𝘮𝘮𝘶𝘯𝘦 𝘳𝘦𝘨𝘶𝘭𝘢𝘵𝘪𝘰𝘯 𝘸𝘪𝘵𝘩 𝘪𝘮𝘱𝘭𝘪𝘤𝘢𝘵𝘪𝘰𝘯𝘴 𝘧𝘰𝘳 𝘵𝘩𝘦 𝘵𝘳𝘢𝘯𝘴𝘭𝘢𝘵𝘢𝘣𝘪𝘭𝘪𝘵𝘺 𝘰𝘧 𝘌𝘶𝘳𝘰𝘱𝘦𝘢𝘯-𝘥𝘦𝘳𝘪𝘷𝘦𝘥 𝘣𝘪𝘰𝘮𝘢𝘳𝘬𝘦𝘳𝘴 𝘢𝘯𝘥 𝘵𝘩𝘦𝘳𝘢𝘱𝘪𝘦𝘴.

💡 𝗧𝗮𝗸𝗲 𝗵𝗼𝗺𝗲 𝗺𝗲𝘀𝘀𝗮𝗴𝗲
• CIMA profiles 10.25 million peripheral blood mononuclear cells from 428 healthy Chinese adults using joint scRNA-seq and scATAC-seq, resolving 73 immune cell states and directly linking transcriptional programs to regulatory chromatin landscapes at scale.
• A deep-learning chromatin language model (CIMA-CLM), combined with cell-type quantitative trait locus mapping, enables inference of expression- and chromatin-associated variants beyond experimentally profiled cells, revealing that most disease-associated variants act through highly restricted immune cell types.
• The asthma-associated variant rs34415530 selectively regulates IKZF4 expression in FOXP3 regulatory T cells, highlighting cell-type-specific genetic control of immune tolerance pathways.
• The East Asian-enriched variant rs11886530 regulates the circadian genes NPAS2 and NR1D1 specifically in T cells and is largely absent from European datasets, illustrating ancestry-dependent regulatory mechanisms.

🔥 𝗜𝗺𝗽𝗮𝗰𝘁
 • By showing that immune regulatory wiring differs between Chinese, European and Japanese populations, this work challenges the assumption that targets, biomarkers, and drug-response models derived from European cohorts are universally valid, with direct implications for precision medicine and immunotherapy development across ancestries.

❓ 𝗢𝗽𝗲𝗻 𝗾𝘂𝗲𝘀𝘁𝗶𝗼𝗻𝘀
 • Which population-specific variants drive clinically relevant immune phenotypes in East Asian cohorts?
 • How can Chinese, Japanese, and European immune atlases be integrated to define shared versus ancestry-specific causal mechanisms?
 • Which sex-associated immune differences translate into divergent responses to vaccines, infections, or immunotherapies?

𝗖𝗵𝗶𝗻𝗲𝘀𝗲 𝗜𝗺𝗺𝘂𝗻𝗲 𝗠𝘂𝗹𝘁𝗶-𝗢𝗺𝗶𝗰𝘀 𝗔𝘁𝗹𝗮𝘀
Jianhua Yin, et al.
Science, January 2026
Corresponding authors: Yanan Cao, Xun Xu, Longqi Liu, Xin Jin, Chuanyu Liu

𝘐𝘭𝘭𝘶𝘴𝘵𝘳𝘢𝘵𝘪𝘰𝘯 𝘢𝘥𝘢𝘱𝘵𝘦𝘥 𝘧𝘳𝘰𝘮 𝘵𝘩𝘦 𝘢𝘳𝘵𝘪𝘤𝘭𝘦

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID are two post-viral diseases, which share many common symptoms and pathophysiological alterations. Yet a mechanistic explanation of disease induction and maintenance is lacking. This hinders the discovery and implementation of biomarkers and treatment options, and ultimately the establishment of effective clinical resolution. Here, we propose that acute viral infection results in (in)direct endothelial dysfunction and senescence, which at the blood-brain barrier, cerebral arteries, gastrointestinal tract, and skeletal muscle can explain symptoms. The endothelial senescence-associated secretory phenotype (SASP) is proinflammatory, pro-oxidative, procoagulant, primed for vasoconstriction, and characterized by impaired regulation of tissue repair, but also leads to dysregulated inflammatory processes. Immune abnormalities in ME/CFS and long COVID can account for the persistence of endothelial senescence long past the acute infection by preventing their clearance, thereby providing a mechanism for the chronic nature of ME/CFS and long COVID. The systemic and tissue-specific effects of endothelial senescence can thus explain the multisystem involvement in and subtypes of ME/CFS and long COVID, including dysregulated blood flow and perfusion deficits. This can occur in all tissues, but especially the brain as evidenced by findings of reduced cerebral blood flow and impaired perfusion of various brain regions, post-exertional malaise (PEM), gastrointestinal disturbances, and fatigue. Paramount to this theory is the affected endothelium, and the bidirectional sustainment of immune abnormalities and endothelial senescence. The recognition of endothelial cell dysfunction and senescence as a core element in the aetiology of both ME/CFS and Long COVID should aid in the establishment of effective biomarkers and treatment regimens.

Un DIU de grande qualité permettant aux internes d’approfondir leurs connaissances en immunologie, enseignement auquel participent bien évidemment les immunologistes mais également tous nos autres collègues notre discipline étant éminemment transversale

Researchers at the Federal University of São Paulo (Unifesp - Universidade Federal de São Paulo) in Brazil have uncovered a previously unrecognized immune-evasion mechanism used by #SARSCoV2, revealing how the #virus directly manipulates host cell #RNA to suppress #antiviral defenses.

▪️ Published in NAR Molecular Medicine, the study shows that beyond conventional immune evasion, SARS-CoV-2 interacts with host RNA in infected #lung cells in a uniquely sophisticated way, disrupting #interferon signaling, a cornerstone of innate #immunity.

▪️ Led by Prof. Marcelo R. S. Briones, the research demonstrates that viral RNA rapidly engages long non-coding RNAs (lncRNAs) - including UCA1, GAS5, and NORAD - immediately after cell entry. Through N⁶-methyladenosine (m⁶A) methylation, the virus alters RNA structure, destabilizing classical base pairing and promoting alternative interactions that weaken RNA-RNA regulation and blunt interferon responses.

▪️ Notably, UCA1 emerged as a central regulatory node, showing altered expression and increased methylation while directly interacting with both the viral #genome and interferon pathway components.

▪️ The work, with key contributions from Cristina Mendes Peter and Caio De Oliveira Cyrino, leveraged Oxford Nanopore Technologies sequencing and #machinelearning analyses to map RNA interactions and methylation patterns in real time, with mathematical support from Fernando Antoneli and Nilmar Moretti.

💡 While fundamentally mechanistic, these findings reshape our understanding of RNA virus #biology and point toward potential therapeutic strategies, including targeting RNA methylation enzymes to restore antiviral immunity.

🗃️ See comments section for reference. | 16 comments on LinkedIn

Un « supermicroscope » révèle en direct l’infiltration des virus de la grippe dans nos cellules
👉👉 L’article dans sa totalité: https://lnkd.in/epE5XRAv
👉👉 Vidéo Youtube: Comment les virus de la grippe pénètrent-ils dans nos cellules ?: https://lnkd.in/e-9Pr88Q
Vers de nouvelles thérapies antivirales plus efficaces et plus ciblées.

Une nouvelle technique de microscopie permet pour la première fois d’observer en direct et en haute résolution le processus par lequel les virus de la grippe pénètrent les cellules. Combinant deux puissants outils d’imagerie, la technique a mis en lumière la manière dont les cellules tentent activement de se défendre avant d’être infectées. La technologie pourrait contribuer au développement de thérapies antivirales plus efficaces et plus ciblées.

Les virus de la grippe utilisent leurs protéines de surface, dites hémagglutinines, pour pénétrer et infecter les cellules. Plus précisément, elles interagissent avec les molécules d’acides sialiques présentes au niveau des glycolipides et des glycoprotéines structurant la surface des cellules. La fixation stable à la surface de la cellule s’effectue par le biais de liaisons multivalentes entre plusieurs hémagglutinines et acides sialiques.

Une enzyme appelée neuraminidase induit ensuite la rupture des acides sialiques, permettant au virus de pénétrer à l’intérieur de la cellule. L’interaction compétitive entre les hémagglutinines et l’enzyme permet au virus de se diffuser latéralement le long de la membrane cellulaire. Il s’agit notamment d’un processus cellulaire dynamique essentiel au fonctionnement des cellules (pour l’absorption de substances vitales telles que les hormones) que les virus détournent afin de les infecter.

La diffusion latérale à la surface de la cellule permet au virus d’identifier le point d’entrée idéal pour la pénétrer, c’est-à-dire la région de la membrane où de nombreuses molécules réceptrices sont regroupées. Une cavité stabilisée par une protéine spécifique appelée clathrine se forme ensuite à cet endroit pour englober le virus à l’intérieur d’une vésicule. Cette vésicule migre vers l’intérieur de la cellule pour se dissoudre, libérant ainsi les protéines virales.

L’observation de ce processus membranaire dynamique est essentielle à la compréhension du potentiel des virus grippaux à infecter les cellules. Cependant, les techniques de microscopie conventionnelles ne disposent pas de la résolution suffisante pour détecter les mouvements de ces virus au niveau des membranes cellulaires, dont l’épaisseur de la bicouche lipidique est d’environ 5 à 10 nanomètres....

Sources :
-How influenza viruses enter our cells: https://lnkd.in/eJ7QErs3
-PNAS - Enhanced visualization of influenza A virus entry into living cells using virus-view atomic force microscopy: https://lnkd.in/exQayP-J

𝗔𝘅𝗼𝗹𝗼𝘁𝗹𝘀 𝗿𝗲𝗴𝗿𝗼𝘄 𝗮 𝘁𝗵𝘆𝗺𝘂𝘀 𝗳𝗿𝗼𝗺 𝘀𝗰𝗿𝗮𝘁𝗰𝗵


🧠 𝗔 𝗽𝗮𝗽𝗲𝗿 𝗮 𝗱𝗮𝘆 𝗸𝗲𝗲𝗽𝘀 𝗯𝗿𝗮𝗶𝗻 𝗱𝗲𝗰𝗮𝘆 𝗮𝘄𝗮𝘆 🧠
Tuesday 30 December 2025

𝘛𝘩𝘪𝘴 𝘴𝘵𝘶𝘥𝘺 𝘴𝘩𝘰𝘸𝘴 𝘵𝘩𝘢𝘵 𝘢𝘹𝘰𝘭𝘰𝘵𝘭𝘴 𝘤𝘢𝘯 𝘧𝘶𝘭𝘭𝘺 𝘳𝘦𝘨𝘦𝘯𝘦𝘳𝘢𝘵𝘦 𝘢 𝘧𝘶𝘯𝘤𝘵𝘪𝘰𝘯𝘢𝘭 𝘵𝘩𝘺𝘮𝘶𝘴 𝘢𝘧𝘵𝘦𝘳 𝘤𝘰𝘮𝘱𝘭𝘦𝘵𝘦 𝘳𝘦𝘮𝘰𝘷𝘢𝘭, 𝘳𝘦𝘷𝘦𝘢𝘭𝘪𝘯𝘨 𝘢 𝘮𝘪𝘥𝘬𝘪𝘯𝘦-𝘥𝘳𝘪𝘷𝘦𝘯 𝘱𝘳𝘰𝘨𝘳𝘢𝘮 𝘵𝘩𝘢𝘵 𝘳𝘦𝘣𝘶𝘪𝘭𝘥𝘴 𝘵𝘩𝘺𝘮𝘪𝘤 𝘴𝘵𝘳𝘰𝘮𝘢 𝘢𝘯𝘥 𝘱𝘰𝘪𝘯𝘵𝘴 𝘵𝘰 𝘯𝘦𝘸 𝘸𝘢𝘺𝘴 𝘵𝘰 𝘳𝘦𝘴𝘵𝘰𝘳𝘦 𝘵𝘩𝘺𝘮𝘪𝘤 𝘧𝘶𝘯𝘤𝘵𝘪𝘰𝘯 𝘢𝘧𝘵𝘦𝘳 𝘥𝘢𝘮𝘢𝘨𝘦 𝘰𝘳 𝘢𝘨𝘪𝘯𝘨.

💡𝗧𝗮𝗸𝗲 𝗵𝗼𝗺𝗲 𝗺𝗲𝘀𝘀𝗮𝗴𝗲
 • Juvenile axolotl regenerates thymus de novo after complete thymectomy, restoring nodule morphology by 35 days post-thymectomy.
 • Single-cell RNA sequencing shows regenerated thymus reconstitutes thymic epithelial cells, T cells, and stromal niches; transplantation proves renewed hematopoietic progenitor cell homing and thymopoiesis.
 • FOXN1 is essential for thymus size and T cell output, yet dispensable for rudiment initiation; MDK (midkine–protein tyrosine phosphatase receptor type Z1) signaling is an early regeneration trigger.

🔥𝗜𝗺𝗽𝗮𝗰𝘁
 • Defines a regeneration-specific midkine axis that could be harnessed to rebuild thymic epithelial niches after thymectomy or involution.

❓𝗢𝗽𝗲𝗻 𝗾𝘂𝗲𝘀𝘁𝗶𝗼𝗻𝘀
 • What is the lineage source of de novo thymic epithelial cells?
 • Can midkine activation restore mammalian thymus after complete ablation?
 • How is self-tolerance enforced without clear corticomedullary architecture?

𝗠𝗼𝗹𝗲𝗰𝘂𝗹𝗮𝗿 𝗯𝗮𝘀𝗶𝘀 𝗳𝗼𝗿 𝗱𝗲 𝗻𝗼𝘃𝗼 𝘁𝗵𝘆𝗺𝘂𝘀 𝗿𝗲𝗴𝗲𝗻𝗲𝗿𝗮𝘁𝗶𝗼𝗻 𝗶𝗻 𝗮 𝘃𝗲𝗿𝘁𝗲𝗯𝗿𝗮𝘁𝗲, 𝘁𝗵𝗲 𝗮𝘅𝗼𝗹𝗼𝘁𝗹
Anna Czarkwiani, Macrina Lobo, Lizbeth Bolaños-Castro, Ph.D. et al.
Science Immunology, December 2025
Corresponding author(s): Rene Maehr, Max H Yun

🔗 𝘓𝘪𝘯𝘬 𝘵𝘰 𝘵𝘩𝘦 𝘱𝘢𝘱𝘦𝘳 𝘪𝘯 𝘤𝘰𝘮𝘮𝘦𝘯𝘵𝘴
🧩 𝘐𝘭𝘭𝘶𝘴𝘵𝘳𝘢𝘵𝘪𝘰𝘯 𝘢𝘥𝘢𝘱𝘵𝘦𝘥 𝘧𝘳𝘰𝘮 𝘵𝘩𝘦 𝘱𝘢𝘱𝘦𝘳 + 𝘚𝘤𝘪𝘦𝘯𝘤𝘦 𝘐𝘮𝘮𝘶𝘯𝘰𝘭𝘰𝘨𝘺 𝘤𝘰𝘷𝘦𝘳 + 𝘮𝘺 𝘤𝘩𝘪𝘭𝘥𝘳𝘦𝘯'𝘴 𝘧𝘢𝘷𝘰𝘶𝘳𝘪𝘵𝘦 #𝘮𝘪𝘯𝘦𝘤𝘳𝘢𝘧𝘵 𝘤𝘩𝘢𝘳𝘢𝘤𝘵𝘦𝘳!

One of the most clinically useful aging markers is hiding in plain sight.
And it isn’t found in your genome.

At the Geneva Longevity Summit, I sat beside two pioneers Steve Horvath and Gordan Lauc, whose work has reshaped how we think about biological time.

The discussion made something very clear:

We are entering the era of immune-aging clocks, and IgG glycans are leading the way.

For decades, we assumed the genome held the answers to lifespan and disease risk.
But the data tells a different story.

Genetics explains only 10-30% of the variance in chronic disease and longevity. The rest comes from the biological systems that change in response to life: epigenetics, metabolism, immune signaling, and inflammation.

That’s where glycans come in.

Glycans are complex sugar structures attached to proteins. They regulate immunity, inflammation, and communication between cells. And because most plasma proteins (including IgG) are glycosylated, the IgG glycome becomes a real-time map of immune aging.

Here is why this matters clinically:

• IgG glycans shift predictably with age.
• This remodeling contributes directly to inflammaging.
• Pro-inflammatory patterns rise. Anti-inflammatory patterns fall.
• Women experience an accelerated shift during perimenopause due to estrogen loss.
• GlycanAge correlates strongly with frailty, metabolic dysfunction, and cardiovascular risk.

And unlike genetics, glycan profiles are reversible.

Lifestyle, sleep, exercise, nutrition, stress load, and hormone therapy, especially estradiol in menopausal women, can all modify glycan age.

Glycans reflect immune balance over weeks to months, are stable enough for clinical decisions, and responsive enough for intervention tracking.

Multiple clinics are piloting GlycanAge alongside lipid panels and HbA1c.

What would you do with a clearer window into your own immune age?

References:
Glycosylation: mechanisms, biological functions and clinical implications. (2024) 
Recent advances in N-glycan biomarker discovery among human diseases. (2024). 
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