“The immune system is an evolutionary marvel, defending us daily against countless microbes. While central immune tolerance was once thought to be the key mechanism of immune regulation, discoveries by Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi revealed the critical role of peripheral tolerance,” Dr Sanjay Singh, CEO of Gennova Biopharmaceuticals told The Indian Express. Scientists and doctors praised their outstanding contributions and agree that they are truly deserving of the 2025 Nobel Prize in Physiology or Medicine. The announcement was made on Monday by the Nobel Assembly at Karolinska Institutet. According to Gaurav Narula, Prof, Paediatric Oncology and Health Science at Tata Memorial Hospital who leads the CAR-T & Cell Therapy centre this discovery marks a pivotal advancement in the field of medicine and has fundamentally transformed our understanding of immunology, particularly immune tolerance. “Traditionally, immunology focused on the central regulation of T cell function. However, we now recognize the complexities of the immune system and that regulation can also occur in the periphery and how they apply to various medical conditions. For example, in autoimmune disorders, the number of regulatory T cells (Tregs) is often reduced, leading to a breakdown in immune tolerance and allowing T cells to attack the body's own tissues. In contrast , in cancer, T regulatory cells play a protective role to the cancer by preventing targeting and eliminating of tumour cells,” Dr Narula said. He added that these insights are reshaping our approaches to diagnosis and treatment across multiple diseases involving the immune system and also to learn to modify these T regulatory cells to develop new cures for cancer and autoimmune disorders. Dr Vineeta Bal, scientist (retired), National Institute of Immunology explained that regulatory T cells play a significant role in various forms of illnesses and help in maintaining homeostasis. “They dampen the so-called highly 'inflammatory' immune responses thereby helping to 'regulate' damage caused by pathogens such as viruses. Loss of balance between pro- and anti-inflammatory responses to SARS-CoV2 infection was a significant contributor to patients of Covid-19, for example, many of whom succumbed to infection. Regulatory cells are like the brakes for a fast moving bicycle. We need speed to bring infection under control, but with minimal damage to the body parts. Helper and cytotoxic T cells function like speeding bicycles whereas regulatory T cells function as an efficient brake,” Dr Bal said. The expert observed that over the years regulatory T cells have been shown to contribute to regulation of many processes in the body including cancer, allergies, autoimmune diseases, going beyond infections. “The contribution of Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi, winners of this year's Nobel prize in Physiology or Medicine was extremely critical for the development of the concept of homeostasis in immunology with a negative feedback loop identified in the form of regulatory T cells. I wonder whether the discoverers ever imagined how important these cells would be as we see today with umpteen publications identifying diversity in their contribution to immune response,” Dr Bal said. Dr Singh added that the Nobel prize winners identified regulatory T cells (Tregs) as key players in preventing autoimmunity. “Their work linked FoxP3 mutations to impaired immune regulation and autoimmune disease. Their contributions have transformed our understanding of immune homeostasis and opened new avenues for treating autoimmune disorders,” Dr Singh added.
