CNC-UC scientists congratulate the Nobel Prize awardees Mary E. Brunkow, Frederick J. Ramsdell and Shimon Sakaguchi “for their groundbreaking discoveries concerning peripheral immune tolerance that prevents the immune system from harming the body. Their discoveries have laid the foundation for a new field of research and spurred the development of new treatments, for example for cancer and autoimmune diseases”, as stated on the Nobel Prize website.

Several CNC-UC scientists have been investigating related matters regarding the imune system. Here are their comments on the distinguished discoveries and how the work of the award winners relates to the work they have been conducting at CNC-UC.

Joana Ribeiro Guedes, Neuronal Circuits and Behavior group | This year Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi were awarded the Nobel Prize on Physiology or Medicine for their groundbreaking discoveries concerning peripheral immune tolerance. For many years, the immune system was considered an "army" that was only active when our body had to fight a foreign pathogen. This view has shifted dramatically following the discovery of T regulatory cells which allow immune tolerance.

These cells are the "sergeants that regulate the army". Not only are they essential to prevent excessive inflammation upon infection, but we now know that, in physiological (non-infection) conditions, they keep in check the function of many other immune cells preventing unnecessary activation. T regulatory cell dysfunction has been consistently shown to contribute to autoimmune disorders, including rheumatoid arthritis, lupus and multiple sclerosis. Importantly, they also play a role in early-life allergies.

In our laboratory, we are studying how immune cells of the meninges, such as innate lymphoid cells type 2, T helper 2 lymphocytes and T regulatory cells contribute to abnormal behaviors reminiscent of Attention-Deficit/Hyperactivity Disorder, the most common neurodevelopmental condition.

This work has been partially funded by the project Th2brain (FCT-funded 2022.02604.PTDC; here).

Eugénia Carvalho, Obesity, Diabetes and Complications group | This is a critical topic that encompasses not only cancer biology but is of at most importance to understander adipose tissue metabolism and physiology. Immune metabolism in adipose tissue, or the recruiting of immune cells to adipose tissue is a relatively new field of study. This is particularly important since some of the cancers, that include liposarcoma, breast cancer, liver and gastric and pancreatic cancer, etc. just to name a few, are linked to obesity or the accumulation of adipose tissue.

Immune cells are recruited to adipose tissue depots throughout the body. We have spent some time trying to understand which immune cells are recruited to adipose tissue in people with obesity. We have assessed participants before and after they have undergone bariatric surgery. Our studies have evaluated cell type, percentages and function, in relation to the same immune cells that are found in circulation.

1. We have evaluated the role of CD8+ Treg cells in obesity and insulin resistance (here).

2. We have identified and characterized the role of less known CD20+ Tcells in adipose tissue and circulation pre and post bariatric surgery (here, here and here).

3. How bariatric surgery impacts alterations in the immune system and observed that high % of Th1 and Tc1 cells infiltrate visceral adipose tissue in people with obesity (here and here).

Immune metabolism differs and maybe regulated depending on the various metabolic phenotypes of a person.

As stated on the award website, “The immune system is a marvel of intricate checks and balances, enabling robust defences against infections while, in most cases, avoiding destructive responses against the body’s own tissues. How is this balance maintained? This question has puzzled immunologists for more than a century. Through a combination of insightful observations and carefully designed experiments, this year’s Laureates of the Nobel Prize in Physiology or Medicine, Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi, made discoveries that provided critical answers. By defining CD4+CD25+FOXP3+ regulatory T cells (Treg cells) and their importance in the control of self-reactive responses, their work decisively launched the field of Treg cell-mediated peripheral immune tolerance. The story is one of scientific curiosity, persistent investigations and critical discoveries that have revolutionized the understanding of immune regulation, with relevance for self-tolerance, autoimmunity and tumour evasion.”

Here you can find the Press Release about the 2025 Nobel Prize in Physiology or Medicine. 

Image: https://www.nobelprize.org/prizes/medicine/