The 2025 Nobel Prize in Physiology or Medicine has been awarded jointly to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their seminal work on peripheral immune tolerance. Their groundbreaking research uncovered the critical role of regulatory T cells (Tregs), particularly the CD4+CD25+FOXP3+ subset, in preventing autoimmune reactions by suppressing immune responses against the body's own tissues. This foundational discovery has reshaped immunology and paved the way for novel therapies targeting autoimmune disorders, cancer, and transplantation. Their findings date back to Sakaguchi's 1995 paper identifying Tregs and were corroborated by Brunkow and Ramsdell’s investigations into autoimmune disease mechanisms.