Immunology

Immunosenescence revisited: from immune decline to immune remodeling through immune resilience and precision assessment of inflammaging.
 
=> Very informative study that helps improve the interpretation of immune parameters in ICU patients, who are often of advanced age, particularly in the context of sepsis.
 
=> Measurements of mHLA-DR, lymphocyte subsets, IFN-γ release, IL-6, CRP, and immature neutrophils in two cohorts of elderly subjects (with and without comorbidities) did not reveal major immune impairments. These findings suggest that immunosenescence, although supported by substantial evidence, remains difficult to capture at the individual level using currently available immune biomarkers.
 
It’s here: https://lnkd.in/dSFUzgja

The Immune System’s Greatest Plot Twist: When Losing MHC Class I Makes Cancer Cells More Vulnerable

For decades, immunology textbooks have taught a simple rule: MHC class I talks to CD8+ T cells. MHC class II talks to CD4+ T cells. End of story. But nature, as always, had other plans. In a stunning discovery published in Nature Immunology, researchers have flipped this paradigm on its head—showing that when target cells lose MHC class I, they become more susceptible to CD4+ T cell attack, not less. Think of it as a burglar cutting the alarm wires, only to accidentally trigger a much deadlier silent alarm.

The team found that MHC I-deficient cells—whether gut cells during graft-versus-host disease or melanoma cells—are exquisitely sensitive to a fiery, iron-dependent form of cell death called ferroptosis. The mechanism is beautifully counterintuitive: without MHC I, cells become hyper-responsive to IFNγ signaling, ramping up lipid peroxidation and iron metabolism pathways that make them prime targets for CD4+ T cell-mediated destruction. In mouse models, MHC I-deficient tumors regressed significantly more when treated with tumor-specific CD4+ T cells. And in human melanoma and colon cancer datasets, patients with low MHC I expression but high CD4+ T cell infiltration had dramatically better survival on immune checkpoint therapy.

This isn't just a cool biology story—it's a potential game-changer for immunotherapy. Tumors that downregulate MHC I to escape CD8+ T cells (classic "immune cold" tumors) might actually be primed for CD4+ T cell attack. The authors suggest that we could design therapies to actively leverage this vulnerability, turning a common escape mechanism into an Achilles' heel. Whether in cancer, transplantation, or infectious disease, this work rewrites the rulebook on how MHC I shapes immune recognition. Sometimes, the best defense… is losing your armor.

#Immunology #CancerResearch #MHCClassI #CD4TCells #Ferroptosis #Immunotherapy #ParadigmShift #NatureImmunology #GVHD #CheckpointInhibitors

https://lnkd.in/gWFySUWm

In science, is anything sweeter than serendipity?

A chance seating arrangement over ten years ago put Martin Wikelski and Christian Kurts side by side at a meeting. As these things go, boredom sparked a casual conversation between the ornithologist and the immunologist. Christian shared a strange story from his immunology lab, thinking it would only be of passing interest to the expert in bird migration beside him.

While studying immune cells in the spleen of mice, Christian’s team had been using a standard technique known as magnetic cell separation. But they kept running into the same problem. There were unwanted cells—macrophages—that kept sticking to the magnet, contaminating their experiments. So, they took a closer look at these pesky cells.

It turns out that those macrophages, which clear red blood cells in the spleen, accumulate ferrimagnetic iron oxides in the process. This, the team found, made them exhibit “superparamagnetism”. In other words, they respond to magnetic fields in a way nobody anticipated for immune cells.

“After telling Martin this story, we realized that macrophages might be a candidate for how cells can sense Earth’s magnetic field,” Christian recalls.

That fortuitous encounter set in motion a study on a fundamental question: how animals navigate through magnetic sensing. The work focused on a classic model of navigation—the homing pigeon—and brought together immunology, physics, and ornithology under the leadership of Clivia Lisowski.

Today, that work is published in Science Magazine. The team reports that pigeons appear to use magnetically responsive macrophages in the liver as part of a broader navigation system, helping them orient when visual cues such as the sun and landmarks are absent on cloudy days.

The team included immunologists from The University of Bonn and the Institute of Molecular Medicine and Experimental Immunology at the Universitätsklinikum Bonn; physicists from the University of Duisburg-Essen; and ornithologists at the Max Planck Institute of Animal Behavior.

Read it here: https://lnkd.in/dx_Pryxd| 17 commentaires sur LinkedIn

Je publie aujourd’hui un nouvel article consacré aux fondations du système immunitaire.

Après une première série centrée sur les cellules Natural Killer (NK) et leurs applications en immunothérapie, j’ai souhaité revenir aux bases de l’immunologie afin de proposer une vision plus globale et structurée du fonctionnement du système immunitaire.

Cet article aborde notamment :
• l’organisation générale du système immunitaire
• les organes et tissus lymphoïdes
• les principes de l’immunité innée et de l’immunité adaptative

Cet article marque la fin de cette série de posters consacrée aux fondations du système immunitaire, avant d’aborder plus en détail les différents acteurs et mécanismes des réponses immunitaires dans les prochaines publications.

Merci à celles et ceux qui suivent et soutiennent ce projet de vulgarisation scientifique.
#Immunologie #SystèmeImmunitaire #Biologie #VulgarisationScientifique

This depiction of viral threats confronting both bacteria and people, and the protein and cellular defenses arrayed against them, illustrates how human immunity traces part of its antiviral arsenal to ancient microbial predecessors.

This shared defensive heritage is already suggesting novel tools for molecular biology and new approaches to medicine.

Learn more this week in Science: https://scim.ag/43rZNM1

💡What if the adaptive immune system evolved not just to fight pathogens — but to manage the intrinsic dangers of multicellular life itself? 💡

In this new Trends in Immunology Opinion article Derick Okwan-Duodu and Edgar Engleman propose a provocative framework: adaptive immunity may have emerged as a “constitutive danger management” system, shaped by mitochondrial mobility, metabolic stress, and the need to preserve tissue homeostasis in complex organisms.

A recommended interesting read 👉 https://lnkd.in/epMdM3Eq

The field of cardiac lymphatic research has expanded considerably over the past decade. Clinical studies have uncovered lymphatic remodelling in a wide range of cardiovascular diseases, and experimental research has demonstrated that these structural alterations often lead to dysfunction of lymphatic transport. Given the vital physiological role of lymphatics, insufficient lymphatic drainage can affect several aspects of cardiac pathophysiology, including myocardial fluid balance, the immune microenvironment, collagen turnover and lipid handling. In this Review, current knowledge on cardiac lymphatics is summarized, including the structural and molecular specializations underlying their diverse homeostatic functions, and how these features can be altered in cardiovascular diseases. The latest research on the effects of inflammation on lymphatics is presented, together with the mechanisms by which lymphatics modulate immunity. The regulation of cardiac lymphangiogenesis is discussed, including accumulating evidence of immune cell–lymphatic crosstalk in the heart, the role of metabolic and biomechanical stimulation of lymphangiogenesis, and examples of experimental approaches to therapeutic lymphangiogenesis and their current limitations. Finally, areas for future research are highlighted, including the translation of lymphatic imaging and lymphangiogenic therapies to the clinic for patients with cardiovascular disease. In this Review, Brakenhielm summarizes current knowledge on cardiac lymphatics, including structural and molecular features of the lymphatic system, the regulation of cardiac lymphangiogenesis, the lymphatic-mediated modulation of immunity and inflammation, and the alterations in cardiovascular diseases, and discusses potential approaches for therapeutic lymphangiogenesis as well as areas for future research.

The liver, a key metabolic organ, has a central role in maintaining systemic homeostasis but is vulnerable to numerous diseases. Its metabolic functions are mainly carried out by hepatocytes; however, the liver also harbours diverse non-parenchymal cell populations, including immune cells. Among these, Kupffer cells, the resident macrophages of the liver, are critical modulators of liver function and immunity. Emerging research highlights their dynamic roles throughout life, from maintaining tissue homeostasis to shaping the balance between immune tolerance and activation in adulthood. Kupffer cells are located in liver sinusoids, where they act as frontline defenders, clearing pathogens and cellular debris from the circulation. Beyond their established phagocytic and immune regulatory functions, Kupffer cells influence metabolic processes, tissue repair and oncogenesis. Moreover, they shape the response of the liver to metabolic disorders such as metabolic dysfunction-associated steatohepatitis, infections and malignancies, including hepatocellular carcinoma. Here we explore Kupffer cell biology, focusing on the development, heterogeneity and multifaceted roles of these cells in liver health and disease. We further discuss how advances in imaging, transcriptomics and macrophage-targeted therapies can inform future strategies to combat liver-associated health challenges. This Review provides an integrated overview of Kupffer cell biology, from their embryonic origin and spatial organization to their functional specialization within the liver. It emphasizes how Kupffer cells act as immune sentinels while also shaping metabolic regulation, tissue repair, infection and cancer and discusses how emerging technologies are refining our understanding of their context-dependent roles across physiological and pathological settings.

The best time to get an infection might be after a meal, suggest experiments in mice and humans that found that certain immune cells, known as T cells, seem to get a boost from food.

The findings, published today in Nature, could identify ways to improve immune therapies, help physicians to decide when to give vaccinations and eventually show how diet can improve immunity.

Source in comments.

🧠 The Immune System's Master Messenger 📱

This image captures a primary human dendritic cell, one of the most important coordinators of the immune response.

With its intricate, tree-like extensions reaching in every direction, a dendritic cell is constantly sampling its environment for signs of infection, cancer, or tissue damage. Once it detects a threat, it processes that information and presents it to T cells, effectively teaching the immune system what to attack.
Think of dendritic cells as the intelligence officers of immunity: they don't do most of the fighting themselves, but they decide when and where the battle begins.

🔬 These cells play a central role in:

- Activating adaptive immune responses
- Cancer immunotherapy research
- Vaccine development
- Autoimmune disease studies

At just a few tens of microns across, this single cell is responsible for helping orchestrate some of the most complex biological decisions in the human body.

Image credit: Dr. Karla Daniels 📸

#Immunology #CellBiology #Microscopy | 11 comments on LinkedIn

Merci médecine/scienves!

Autophagy is a highly conserved, finely regulated and lysosome-dependent biological process through which eukaryotic cells mobilize metabolites in response to nutrient deprivation and dispose of supernumerary or toxic cytoplasmic entities to ensure cellular quality control. In line with the notion that autophagy globally preserves cellular homeostasis, defects in the molecular machinery for autophagy generally favour malignant transformation. Conversely, proficient autophagic responses are often beneficial to developing tumours as they support the survival of malignant cells facing harsh microenvironmental conditions. Finally, the ability of neoplastic cells to undergo autophagy influences their susceptibility to anticancer immune responses in a context-dependent manner. Thus, although autophagy stands out as a major target to intercept cancer at multiple inflection points of the disease, one-size-fits-all approaches are inherently incapable of capturing the complex influence of autophagy on the cancer cell (immuno)biology as a whole. Further complicating this scenario, healthy cells, including tumour-targeting immune effectors, rely on autophagy for their maturation, survival and functions, and pharmacological autophagy inhibitors currently available for use in humans are intrinsically nonspecific. Here, we discuss the promise and limitations of targeting autophagy to limit malignant transformation, exacerbate cancer cell death as driven by conventional therapeutics and restore immunosurveillance in support of superior disease responses to immunotherapy. Autophagy has a highly complex and context-dependent role in cancer, challenging the development of autophagy-modulating strategies. This Review discusses the potential of targeting autophagy to counteract malignant transformation, prevent disease progression and enable anticancer immunosurveillance. Existing and emerging pharmacological strategies and the associated limitations are critically presented.

Exercise is an “underused lever for immune health,” write Pitt Immunology's Marlies Meisel and PMI graduate student Catherine Phelps in a new review published in Immunity by Cell Press.

They synthesize the latest evidence on how exercise affects the immune system and how it varies depending on disease context, training type, and the molecular signals—exerkines—that muscle, fat, and gut microbiota release in response to physical activity. The same training that boosts antitumor immunity can suppress inflammatory programs in autoimmune disease.

Harnessing the power of exercise—including personalized exercise prescriptions and exerkine-based therapeutics for patients unable to train—for treating cancer, autoimmunity, and other diseases will require more research to understand the underlying mechanisms and strong bench-to-bedside collaborations.

Read the full review: https://lnkd.in/dp-dzTvB

T Cell Receptor Signaling and Immune Tolerance: From Autoimmunity to Cancer Immunity.
Tanaka A, Sakaguchi S. Annu Rev Immunol. 2026 Apr;44(1):497-526. doi: 10.1146/annurev-immunol-082724-025403. Epub 2026 Mar 2. PMID: 41770842.
Severe Signal Defect (Immunodeficiency) ↔ Moderate Defect (Systemic Autoimmunity) ↔ Physiological Range (Homeostasis) ↔ Attenuated Signal (Cancer Immunity)

A new ‘K’ind of T helper cell

- Effector CD4+ T helper cell subsets are essential for a range of immune functions, such as orchestrating effector responses, enabling antibody class switching, and maintaining immune homeostasis.

- Cytotoxic CD4+ T lymphocytes (CD4-CTLs) were first described over 40 years ago and initially considered an artifact of in vitro culturing conditions.

- Subsequent studies have provided increased clarity as to the immunological importance of CD4-CTLs and they have now been identified in the contexts of infection, cancer and autoimmunity.

- Here, the authors identify THK cells, a CD4-CTL subset characterized by the co-expression of granzyme K (GZMK) and EOMES. These cells are highly prevalent in ulcerative colitis in addition to cancer, neuroinflammation and chronic viral infection.

- Notably, the authors show that ablation of EOMES in CD4+ T cells reduces colitis severity in mouse models, highlighting THK cells as potential therapeutic targets in immune-mediated disease.

- This study provides a foundation for subsequent investigations into the environmental factors that drive the generation of THK cells and potential strategies to modulate THK cell responses for therapeutic benefit.

https://lnkd.in/eeqjGURM
https://lnkd.in/eV94eS5Q

#immunology #science #inflammation #Tcells #autoimmunity

Recent findings have identified a novel mechanism by which HIV-1 can infect resting T-cells, challenging longstanding assumptions in HIV biology. The research demonstrates that direct cell-to-cell spread of HIV triggers a molecular signaling cascade, temporarily unlocking the nuclear pore complex and allowing viral entry into the nucleus without requiring T-cell activation. This insight provides a new explanation for the persistence of the latent HIV reservoir and highlights potential avenues for targeting these reservoirs. Additionally, the study uncovers new aspects of nuclear transport regulation in immune cells, with broader implications for immunology and therapeutic development.

Tissue-resident regulatory T cells: modulators of local immunity

What is unique about the immune system of people who live to extreme old age? A Review in Nature Reviews Immunology explores how centenarians modulate key hallmarks of immune ageing across innate and adaptive immune compartments.

Read the Review: https://lnkd.in/egQeexbX

In a 2025 #ScienceReview, researchers examined the influence that biological sex exerts on the immune system and immune-related diseases.

Learn more on #DayOfImmunology: https://scim.ag/4s24HdI