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). 
| 25 comments on LinkedIn

Architecture of the neutrophil compartment

- Millions of neutrophils are produced every day by the bone marrow through a well-defined series of differentiation steps before their release into the circulation as terminally differentiated, non-proliferative cells that eventually infiltrate most tissues.

- Neutrophils exhibit remarkable phenotypic and functional diversity across tissues and disease, yet the lack of understanding of how this immune compartment is globally organized challenges translation to the clinic.

- Here the authors performed single-cell transcriptional profiling of neutrophils spanning 47 anatomical, physiological and pathological scenarios to generate an integrated map of the global neutrophil compartment in mice which was named NeuMap.

- NeuMap reveals that neutrophils organize in a finite number of functional hubs that distribute sequentially during maturation to then branch out into interferon-responsive and immunosuppressive states, as well as a functionally silent state that dominates in the healthy circulation.

- TGFβ, IFNβ and GM-CSF push neutrophils along the different trajectories, while transcription factor JUNB controls angiogenic and immunosuppressive states and promotes tissue revascularization.

- The architecture of NeuMap appears to be conserved across sex, environmental and genetic backgrounds, as well as in humans.

- Limitation of the study: relatively small number of pathophysiological conditions analysed. Perturbations associated with allergy, autoimmunity, mucosal inflammation or diseases associated with old age as well as developmental processes remain uncharted in NeuMap.

-  This study delineates the global architecture of the neutrophil compartment and establishes a framework for exploration and exploitation of neutrophil biology.

https://lnkd.in/eh-hw66V

#immunology #science #singlecell #omics

Stanford scientists have discovered that cancer cells don’t just use one trick to hide from the immune system—they use two separate “don’t-eat-me” signals to stop macrophages from killing them.

The first signal, CD47, was already famous for acting like an invisibility cloak that tells macrophages to back off, and blocking it with an anti-CD47 antibody is already in human trials.

In the Nature Immunology paper, the same Stanford team also found that tumors use MHC class I as a second stop signal by binding to a macrophage receptor called LILRB1, which suppresses the macrophage’s ability to engulf and destroy the cancer.

When researchers blocked both CD47 and LILRB1 in mice, tumors rapidly filled with immune cells, shrank significantly, and became far easier for the body to clear.

This shows that many cancers survive by running two overlapping escape systems, and turning off both “don’t-eat-me” pathways at once may dramatically boost the immune system’s ability to attack and eliminate tumors. | 17 comments on LinkedIn

Epigenetic and metabolic programming of innate immune cells shapes host defense and disease susceptibility.

Venez découvrir en avant première notre Livret d'Immunologie sur notre stand, ouvrage à destination des élèves en primaire. Il sera bientôt disponible sur notre site internet et sera distribué gratuitement aux enfants par les ambassadeurs de l'immunologie, qui présentent notre belle discipline, à l'occasion de la journée de l'immuno (qui est le 29 avril).

SFI Société Française d'Immunologie
#Immunologie
#vulgarisation
#science
#livre
#systèmeimmunitaire

TIMC Lab
Université Grenoble Alpes | 18 comments on LinkedIn

Immunometabolism, the intersection of cellular metabolism and immune function, has revolutionized our understanding of T cell biology. Changes in cellular metabolism help guide the development of thymocytes and the transition of T cells from naive to effector, memory and tissue-resident states. Innate-like T cells are a unique group of T cells with special characteristics. They respond rapidly, reside mainly in tissues and express T cell receptors with limited diversity that recognize non-peptide antigens. This group includes invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells and some populations of γδ T cells. Different subsets of innate-like T cells rely on specific metabolic pathways that influence their differentiation and function and distinguish them from conventional CD4+ and CD8+ T cells. Although there are differences between innate-like T cell types, they share metabolic and functional features. In this Review, we highlight recent research in this emerging field. Understanding how metabolic programmes differ between innate-like T cells and other T cells may open opportunities for tailoring innate-like T cell responses and adoptive T cell therapies for use in cancer, metabolic and autoimmune diseases. Functional and metabolic properties of innate-like T cells — namely, iNKT cells, MAIT cells and some γδ T cells — differ from those of conventional T cells. This Review describes how metabolic pathways support innate-like T cell properties such as acquisition of effector capability in the thymus, rapid responsiveness, tissue persistence, antigen adaptation and functional flexibility.

The Nobel Prize in Physiology or Medicine 2025 was awarded to Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi “for their discoveries concerning peripheral immune tolerance.”

Human tumour cells express mutated and non-mutated proteins that can be processed and presented by these cells as peptides bound to human leukocyte antigen (HLA). Some of these peptides are recognized by cognate T cell receptors as ‘non-self’, leading to specific killing of tumour cells by T cells. This process is fundamental to the success of cancer immunotherapy, which exploits the ability of the immune system to eliminate transformed cells. Mutated antigens (neoantigens) have been implicated in the remarkable therapeutic efficacy of immune checkpoint inhibitors (ICIs), which boost endogenous antitumour immune responses. In recent years, the combination of ICIs with personalized cancer vaccines that target neoantigens and other tumour-specific antigens has emerged as a new therapeutic strategy. However, the robust immune pressure that ICIs exert on cancer cells inevitably amplifies the phenomenon of immune editing, which can allow cancer cells to develop resistance mechanisms that subvert surveillance by the immune system. Diminished antigenicity can be due to defects in the antigen processing and presentation machinery, such as HLA-I/II loss of heterozygosity and loss of functional β2-microglobulin. This poses a considerable challenge for combination therapies that include ICIs and for the design of cancer-specific vaccines. Effective tumour-specific T cell immunity — and the success of cancer immunotherapies — relies on the presentation of antigens via human leukocyte antigen (HLA) molecules. In this Review, Bassani-Sternberg and Huber explore recent advances in understanding the repertoire of tumour-specific antigens, as well as how disruptions in antigen processing and presentation contribute to immune evasion and resistance to immune checkpoint blockade. The authors also highlight how these insights can inform the design of personalized neoantigen-based vaccines and combination therapies aimed at outpacing tumour immunoediting.

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

Immunology is the most human—and the most beautiful—of disciplines. Thanks to B Andrade and M Araujo-Pereira for this very pertinent parallel.

This recent PNAS paper is making headlines. Why? Because it focuses on something extremely familiar - Tattoos!

Researchers explored how tattoo ink interacts with the immune and lymphatic systems and clearly demonstrated that its effects do not occur only at the tattoo's site. Instead, it can have a significant, long-term impact on the draining lymph nodes, which affect immune responses to events like vaccines and potentially many other situations as well.

Particularly relevant in a world where nearly 1 in 3 people is likely to have at least a tattoo. And a great example of how science can talk so directly to the general public when it feels familiar. 

If you want to even begin to really understand how cells work, you need to watch this video first; and then reread all the static imagery text books of biochemistry & molecular biology again with fresh eyes. Excellent video Simon Reid.
#highereducation

A roadmap for defining “extrafollicular” B cell responses

Long-lived plasma cells (LLPCs), which continuously secrete antibodies, play a central role in humoral immunity and form the foundation of effective vaccin

The College’s Clinical Immunology Workforce Report finds critical staff shortages across services that diagnose and treat allergies, autoimmune diseases and immunodeficiencies.
 
Three quarters of UK immunology services report that they do not have enough staff to meet current clinical demand.
 
Dr Patrick Yong, Chair of the College Specialty Advisory Committee for Immunology, quotes:

"This is a sobering report. Many services rely on goodwill and unpaid overtime to keep running. We urgently need to establish more training posts and focus on retaining experienced consultants to ensure safe, effective patient care.”

Patients are facing delays to diagnosis and treatment, while consultants are at risk of burnout. The College is calling for more training posts, better support, and improved workforce planning.

Read the full report and recommendations on our website. https://lnkd.in/eyavzHsp