Redefining immune science: From diabetes to Alzheimer’s

Diane Mathis, PhD, has transformed our understanding of diabetes through decades of influential research. Backed by a new $2.25 million grant from the Freedom Together Foundation (formerly the JPB Foundation), she and her team are expanding on this body of work, pushing into new territory that links immune regulation not only to diabetes but also to neurodegenerative diseases like Alzheimer’s.

With the foundation’s sustained support, Mathis has made pivotal discoveries about regulatory T cells, or Tregs—specialized immune cells that help keep inflammation in check. Her team was the first to identify Tregs in fat tissue and has since highlighted their presence in muscle and the brain’s protective layers. These “tissue-Tregs” play crucial roles in metabolic stability and help tissues repair themselves and adapt to challenges such as disease and aging.

The new grant will enable Mathis, the Morton Grove-Rasmussen Professor of Immunohematology in the Blavatnik Institute at Harvard Medical School, and her team to explore three key areas: how Tregs in the brain’s meninges might influence Alzheimer’s disease, how exercise or injury prompts beneficial Treg activity in muscle, and the roles of different Treg subtypes in fat tissue.

A driver of these advances has been Mathis’ collaborations with other scientists, fostered by the foundation. “These interdisciplinary partnerships have greatly enriched our science, both experimentally and theoretically,” Mathis says. She cites joint efforts with Bruce Spiegelman, PhD (Dana-Farber Cancer Institute), on exercise and metabolism, as well as with David Holtzman, MD (Washington University School of Medicine in St. Louis), on neuroimmune mechanisms in Alzheimer’s disease. “Having perspectives from both neuroscience and immunology strengthens our collaborative program,” she adds. Additionally, she highlights her work with Gavin Dunn, MD, PhD, and Brad Hyman, MD, PhD (both from Massachusetts General Hospital), to obtain human brain tissue for translational studies.

Mathis describes this new research phase as an opportunity to “more specifically augment the Tregs best adapted to the job they need to perform. It can be thought of as Treg ‘precision medicine.’” Interest in Tregs is rising rapidly, with companies exploring them as targets for next-generation therapies for metabolic, autoimmune, and neurological diseases. “I’ve co-founded three Treg-based companies, each exploring distinct ways to boost or engineer Tregs as therapies,” Mathis notes.

The Freedom Together Foundation believes the struggle to defend and expand multiracial democracy is the defining challenge of our time.

For the Freedom Together Foundation, supporting Mathis’ work aligns with its broader effort to build a future where all people can thrive. “Dr. Mathis’ innovative investigations are driven by a deep commitment to enhancing the health of our communities,” says Deepak Bhargava, AB ’90, president of the foundation. “Her pioneering contributions are a testament to why the Freedom Together Foundation continues to invest in bold ideas and people who can make them a reality.”

While the foundation’s mission has expanded to center on safeguarding and expanding democracy, medical discovery remains central. “Both a strong democracy and medical research are indispensable to human flourishing. And science and democracy are much more intertwined than most people realize,” Bhargava says.

Mathis credits the foundation’s long-term, flexible funding—and its focus on collaboration across disciplines—with sparking many of her lab’s breakthroughs: “We would never have taken on these additional scientific challenges were we not part of the Freedom Together Foundation family. Thirteen years of funding from the foundation has been game-changing for our lab.”