Immunology

Evolutionary conservation analysis reveals a primordial function of STING as a regulator of lipid metabolism via FADS2 et félicitations à Jenny BERTHELOT (Nguyen).

Spatial compartmentalization and the organization of immune cells into specialized immune niches dictate whether the tumor microenvironment supports or suppresses cancer immunity, holding greater predictive power for clinical outcomes and immunotherapy response than mere immune cell infiltration.

·    Immune Triads (CD8+ T cells, CD4+ T cells, and APC): These compact three-cell hubs enable vital cell-contact cross-talk that prevents T cell exhaustion, supports progenitor exhausted T cells, and drives CD8+ effector differentiation upon immune checkpoint blockade.

·    Stem Lymphoid-Myeloid Niches: Perivascular multicellular reservoirs driven by the CXCL9/10-CXCR3 and CCL19/21-CCR7 axes shelter progenitor exhausted T cells, fueling sustained antitumor responses and predicting favorable immune checkpoint blockade outcomes.

·    Nonstem Lymphoid-Myeloid Niches: Often dominated by tumor-associated macrophages in inner or hypoxic regions, these hubs foster suboptimal signals and metabolic shifts that drive T cell dysfunction, terminal exhaustion, and therapy resistance.

·    Tertiary Lymphoid Structures: Highly organized, ectopic lymphoid factories featuring germinal centers that orchestrate local B cell class switching, somatic hypermutation, antibody production, and long-term immune surveillance.

Nadine Slingerland, Eline Runderkamp, Daniela S. Thommen. 2026. Immune Niches in Cancer. Annual Review of Immunology 44:553-582. https://lnkd.in/gJHGY7rt

While reading about B and T cell receptor diversity for my current project, a question came to mind from a computational perspective.

We have an incredibly diverse repertoire of immune receptors, but I started wondering: Could there be a peptide that none of our TCRs can recognize?

That question first took me to an interesting PNAS paper:
https://lnkd.in/gD_NVk2M

I was curious about the numbers. How many immune cells do we actually have? The study estimates around 1.8 trillion immune cells, including about 760 billion lymphocytes and 500 billion T cells in a reference individual. It is a really interesting paper if you enjoy looking at biology from a quantitative perspective.

While exploring this question further, I came across another fascinating concept: “holes in the T-cell repertoire.”

I’m currently reading more about it and will share what I learn in the next posts.

#Immunology #Bioinformatics

CD4 CTLs in supercentenarians: Signs of adaptive expansion in healthy aging

Research on supercentenarians—people aged 110 and older—reveals that their exceptional longevity and resistance to age-related diseases like cancer may be linked to a specialized population of immune cells known as CD4 cytotoxic T lymphocytes (CD4 CTLs). While these killer cells typically make up less than 5% of T cells in younger individuals, their numbers increase dramatically around age 100, accounting for roughly 10% of T cells in centenarians and 18% in supercentenarians. Genetic profiling shows that these cells undergo significant clonal expansion—cloning themselves into large populations of identical cells—in response to persistent antigen triggers, with receptor sequences matching those found in cancer patients, particularly those with lung cancer. Although these findings suggest that CD4 CTLs adaptively expand to suppress tumor growth or clear senescent cells, experts caution that direct tumor-killing activity in these individuals remains to be proven, as the precise targets and tissue destinations of these expanded immune cells are still under investigation. The original article was published in Cell Rep https://lnkd.in/d65eeX4n and a commentary in Nature https://lnkd.in/d3ysVud8

#genetics #genomics #epigenetics #epigenomics #precisionmedicine #genomicmedicine #dna #rna #brain #neurology #neuroscience #neurodegeneration #neuroinflammation #inflammation #immunity #aging #longevity #cognition #alzheimer #parkinson #movementdisorders #raredisease #dementia #autism #geroscience #ai #bioinformatics #lysosomalstoragedisease #psychiatry #neurodevelopment #neurogenesis  #metabolism #lysosome #mitochondria #autophagy #omics #lipids #lipidomics #cellbiology #microbiome #metagenome #regenerativemedicine #environment #pollution  #publichealth #physiology #biobank #health #drugs #drugrepurposing #drugdiscovery #drugdevelopment #biomarkers #therapeutics #biotechnology #innovation #research #science #sciencecommunication Instituto de Ciencias e Innovación en Medicina (ICIM UDD)

🔬 Why aren't T cells used more often as correlates of protection?
Correlates of protection are measurable biomarkers that can reliably predict protection against infection or disease. T cells have been identified as correlates of protection in a number of infectious diseases, yet they remain underutilised compared with antibody-based measures. As previously highlighted in npj Vaccines:
"T-cell assays are generally harder to perform and to standardise, contributing to a scarcity of T-cell data relative to antibody data in the correlates field." 🔗 https://rdcu.be/fvs1V
 
⚙️ Scaling up T cell testing
Addressing this challenge is exactly why ImmunoServ developed the Immuno-T® assay: a simple, scalable and standardisable approach to measuring antigen-specific T cell responses.

🌍 Real-world impact
During the COVID-19 pandemic, Immuno-T® helped generate key insights into both natural immunity and vaccine-induced immune responses.

🔭 Looking ahead
We're now developing and evaluating Immuno-T® test kits for a range of infectious diseases, including:
✅ Seasonal influenza
✅ Avian influenza (bird flu)
✅ Group A Streptococcus (Strep A)

🤝 Interested in a bespoke solution?
If you're investigating correlates of protection and need a reliable way to measure T cell immunity, we'd love to discuss how a bespoke Immuno-T® assay could support your research programme.

Ever wondered why vertebrates developed an adaptive immune system when invertebrates do pretty well without one?

Caetano Reis e Sousa argues that just because adaptive immunity is now crucial for protection against infection in vertebrates, we shouldn't assume that was its original function.

https://rdcu.be/fAz5L

Macrophages are essential components of the innate immune system and have crucial roles in host defence, tissue homeostasis and inflammation. Embryonic macrophages are specialized populations of macrophages that arise early during development and contribute to tissue organization, immune system development and homeostasis. These cells originate from yolk sac and fetal liver progenitors and colonize various tissues during embryogenesis, becoming long-lived tissue-resident macrophages. In the embryo, macrophages are involved in a wide range of developmental processes, including the clearance of apoptotic cells, regulation of organogenesis and establishment of tissue integrity. They are also pivotal in the early establishment of immune tolerance and in the development of the fetal haematopoietic and immune systems. Plenty of literature covers the role of yolk sac-derived macrophages in adult tissues, whereas less is known about their functions in the embryo itself. This Review highlights our emerging understanding of embryonic macrophages, their origin and their roles in organogenesis and development in mice and humans. This Review discusses the origins and roles of macrophages in embryonic development. The authors highlight the importance of macrophages for development of the haematopoietic and immune systems and for the establishment of immune tolerance in early life.

[SAB Voices] "Immunology is everywhere." 🧬

For Professor Jean Daniel Lelièvre , immunology is no longer confined to infectious diseases or rare immune disorders.

From metabolic diseases to cancer and chronic inflammation, it provides a new lens to understand how many diseases develop, and how they can be treated.

In this new episode of SAB Voices, he explains why Marseille already has the scientific, clinical and academic ecosystem needed to make the Marseille Immunology Biocluster a success.

Watch the video to hear his perspective on the growing role of immunology in medicine. 👇

Follow the SAB Voices series to hear from the experts helping shape the future of immunology.

Increased TRAILshort expression is linked to infectious viral diseases and cancer. We previously identified TRAILshort as a dominant-negative TRAIL receptor ligand that confers resistance to full-length TRAIL-induced apoptosis, which is detected in HIV-infected cell cultures and plasma from HIV+...

This review does not aspire to provide comprehensive coverage of any particular area. Rather, it is an attempt to reconsider and summarize the results produced by our team in the field of TCR repertoires over the past 15 years, and to correct som

Excited to share our new paper published in Nature Immunology :

“Microbial adhesion promotes Piezo1 activation to initiate innate immunity”

In this study, we show that microbial adhesion to myeloid cells can act as an early danger signal, activating the mechanosensitive ion channel Piezo1 and triggering LTB4 production. This initiates an IL-1α–CXCL1–dependent wave of neutrophil recruitment before the later, canonical TLR-driven response.
Our findings reveal a previously unrecognized role for mechanotransduction in the initiation of immune responses to infection and highlight important parallels between infectious and sterile inflammation.

Many thanks to everyone in my lab, all our collaborators, and our colleagues who made this work possible!

Read the paper: https://lnkd.in/dZ5r66tZ

Giulia Stucchi Marco Galli Stefano Cozzi Anna Celant Francesca Colnaghi Laura Marongiu Marina Vai Alessandra Polissi Alessandra Martorana Simona Barresi Renato Ostuni Metello Innocenti

Università degli Studi di Milano-Bicocca Dipartimento di Biotecnologie e Bioscienze - UNIMIB Nature Portfolio
#Immunology #InnateImmunity #Infection #Mechanobiology #Piezo1 #Neutrophils #NatureImmunology | 10 comments on LinkedIn

Interleukin-18 (IL-18) is a pleiotropic cytokine of the IL-1 family that has an important role in antitumour and antiviral immunity. Growing interest in its therapeutic potential has led researchers to explore strategies that harness IL-18 to modulate the tumour microenvironment. For example, engineered T cells are being armoured with IL-18 to enhance adoptive cell therapies and strengthen other immunotherapy approaches. As these strategies move towards clinical application, a key translational challenge is identifying the molecular mechanisms that influence treatment response and resistance, crucial for guiding trial design and patient selection across tumour types. This Review revisits the fundamental biology of IL-18, including its origins, cellular sources and regulatory networks, particularly those involving IL-18 binding protein (IL-18BP) and IL-37. We discuss how IL-18 promotes interferon-γ (IFNγ) production within the tumour microenvironment, supporting M1-like macrophage polarization, CD8+ cytotoxic T cell and CD4+ T helper 1 cell responses, natural killer cell activity and durable T cell memory. We also discuss preclinical models of IL-18 delivery, including dendritic cell platforms and cellular therapies, and highlight emerging strategies such as IL-18BP blockade and IL-18-secreting CAR T cells. Finally, we review results from early clinical studies and outline key challenges for translation, including the dual protumour and antitumour roles of IL-18. Interleukin-18 (IL-18) shapes tumour immunity through tightly regulated, context-dependent effects on T cells, NK cells and the tumour microenvironment. Emerging therapeutic strategies, including engineered cellular therapies and decoy-resistant variants, aim to harness IL-18 signalling to enhance antitumour responses while overcoming regulatory constraints.

"We cannot know in advance which observations, hypotheses or technologies will transform our understanding, yet we ... ask scientists to justify the importance of discoveries before they have been made"

As Laura Mackay points out, the immune system would fail if every lymphocyte had to justify its existence from the outset. Just as lymphocyte receptor diversity is an investment against future challenge, we should view the diversity and sometimes inefficiency of scientific research as a price well paid for the potential to make unpredictable, surprising discoveries.

https://rdcu.be/fBW6W

Men and women don’t just have different immune systems—they also age completely distinct.

I am proud to share research by my PhD student, Reza Gheitasi, together with a dedicated interdisciplinary team.
What began during the early COVID-19 pandemic as a high-dimensional immunophenotyping sub-study within our population-based CoNAN cohort in Thuringia has now developed into a translated framework on the sex-dimorphic biology of immune aging.

Conventional aging studies rely on arbitrary age brackets (e.g., "<50" vs. ">65"). In our primary study published in iScience (Cell Press), we analyzed 231 healthy individuals across a continuous lifespan from 19 to 93 years using 30+ marker mass cytometry and non-parametric spline regression.

This continuous modeling revealed, for the first time, distinct age × sex interactions across the lifespan:
Men: Significantly earlier and deeper decline in naive T cells, along with a faster inversion of the CD4:CD8 ratio.

Women: Maintain a better-preserved pool of naive CD8+ T cells and memory B cells well into middle and older age.

Men Face Higher Vulnerability to Infections:
Accelerated exhaustion of naive T cells and the loss of critical co-stimulatory receptors (like CD28) mean older men are less equipped to mount de-novo responses against novel viral and bacterial pathogens. This also explains why older men often exhibit less durable vaccine responses, pointing to a need for adjusted booster schedules or tailored adjuvants.

Women Face Higher Risks of Autoimmunity:
The female immune system is biologically up to a decade "younger" than that of chronological age-matched men. Enhanced by estrogen and higher X-linked TLR7 gene dosage, women mount more potent initial antiviral interferon responses. However, this heightened baseline readiness comes with a trade-off: a higher predisposition to chronic inflammation (inflammaging) and age-related autoimmune diseases.

🎯 The Bottom Line: Moving Beyond "One-Size-Fits-All"
Current public health guidelines and vaccination recommendations are still largely anchored to a single parameter: chronological birth year.
Immunosenescence is not a uniform decline. To optimize prevention and therapy in an aging society, medicine must move toward precision immunology—incorporating sex- and age-stratified vaccination regimens, dose calibrations, and targeted interventions tailored to an individual’s true biological immune state.

📖 Read both open-access papers here:
Cohort Study (iScience, Cell Press): https://lnkd.in/eJzumS9G

Perspective & Clinical Synthesis (npj Aging, Nature):
https://lnkd.in/eYcg4vNt

#PrecisionMedicine #HealthyAging #Immunosenescence #Vaccines #SexDifferences #TranslationalResearch #AcademicMentorship #LifeSciences
Claudia WaskowIrit Nachtigall, Univ. Prof. Dr.Carsten WatzlDeutsche Gesellschaft für Geriatrie (DGG)Deutsche Gesellschaft für Immunologie e.V. (DGfI)Ole Wichmann | 11 comments on LinkedIn

A 2025 #ScienceReview offers an overview of recent research that reveals the immune system not only defends the body but also actively shapes and supports various life-sustaining processes through dynamic, reciprocal interactions with other physiological systems.

Learn more: https://scim.ag/3U56F0v #ScienceMagArchives

The intricate balance of immune reactions towards invading pathogens and immune tolerance towards self is pivotal in preventing autoimmune diseases, wit

The recent Executive Order on childhood vaccines promotes narratives that are not supported by the weight of scientific evidence and will make it harder for families to protect their children against preventable diseases, illnesses, and death.

AAI opposes the Executive Order and has released a statement addressing five key points:
1. Splitting the MMR vaccine increases, rather than reduces, the total number of vaccine doses
2. More visits to the doctor mean greater costs and barriers for families 
3. The Executive Order creates complexity without demonstrated benefit
4. The suggestion that children receive "too many vaccines" misrepresents the science
5. The Executive Order reinforces longstanding misinformation about vaccine safety

Parents deserve accurate information grounded in rigorous science to protect their children. AAI continues to support the childhood vaccines and immunization schedule recommended by the American Academy of Pediatrics.

🔗 Read the full AAI Statement here: https://ow.ly/Q8Rh50ZAzzA

One of the biggest threats to human wellbeing are viral infections and the resistance these viruses are able to develop against the human immune system.

It is not for luck that humans among other mammals have been able to survive millions of years always becoming more adaptable and developing new means of resistance towards parasites.

Scietists have found that much of our genetic material necessary for our immune system and the development of efficient resistance against viruses comes from ancient bacterial DNA. These shared forms of immunity include: cGAS–STING, inflammasomes, argonautes and viperin.

With viruses always mutating and developing new strands, one of the main healthcare emergencies is to develop new treatments against viral infections.

But how can you know your degree of immunity? To identify how your genetics may influence immune function, find vulnerabilities, and help you take action against pathogens, subscribe to ENAble —the startup working to create the branch between genetics and personalized health plans.

#Immunity #EnableDNA #GENETICS
#PersonalizedHealthPlan

https://lnkd.in/emyAf95s

[SAB Voices] Making immunology more accessible starts with education 🧬

Immunology is transforming medicine. Yet for many students, it remains one of the most complex disciplines to master.
Professor Jean Daniel Lelièvre believes that needs to change.

As a physician, researcher and educator, he has spent his career helping bridge the gap between fundamental science and clinical practice. He also sees education as a key ingredient for the future of immunology, ensuring the next generation of clinicians and researchers can translate discoveries into better patient care.

This ambition is at the heart of MIB's commitment to education through initiatives such as ImmunoSkills, which bring together academia, research and industry to develop the skills needed for tomorrow's immunotherapies.
In this new SAB Voices article, Jean-Daniel Lelièvre discusses the expanding role of immunology across medicine, the importance of education, and why Marseille offers the right environment to train the next generation while accelerating research and innovation.

Read the full article 👇

Researchers have uncovered previously unrecognised diversity in the way resident macrophages develop in the peritonea