Autoimmune Disease, Obesity Link Found in Subset of Immune Dendritic Cells

In a recent study published in the journal Immunity, researchers at the Weizmann Institute of Science in Israel reported the findings that a small subtype of immune dendritic cells plays a role in the prevention of both metabolic syndrome and autoimmunity. The study is entitled “Perforin-Positive Dendritic Cells Exhibit an Immuno-regulatory Role in Metabolic Syndrome and Autoimmunity.”

Metabolic syndrome is an obesity-related disorder linked to hyperglycemia (high blood glucose levels), insulin resistance, high blood pressure, and high cholesterol levels. It was previously shown in mice fed a high-fat diet that the immune system plays a role in the development of metabolic syndrome and obesity. Now, according to a press release from the Weizmann Institute, using mice fed a regular diet, researchers assessed the immunological mechanisms that underlie the metabolic syndrome, focusing specially on dendritic cells, important antigen-presenting cells of the immune system that act as sentinels and can trigger an immune response.

The team studied a rare subpopulation of dendritic cells that is rich in perforin-containing granules (perf-DCs; perforin is a killing protein able to create pores on target membranes). Through bone marrow transplantation, the team created animals lacking perf-DCs, and found that these mice progressively gained weight and developed symptoms of metabolic syndrome.

Mice lacking perf-DCs were found to have abnormally high levels of inflammation-causing immune T cells in their fat tissue. Interestingly, when these T cells were removed, the animals did not grow obese. The findings led the authors to suggest that perf-DCs can regulate the levels of certain T cells, controlling them and preventing the development of metabolic syndrome.

Remarkably, a similar effect for perf-DCs on inflammatory T cells was also observed in the experimental autoimmune encephalomyelitis (EAE) model, a mice model of human multiple sclerosis. EAE animals lacking perf-DCs were found to be more prone than usual to develop multiple sclerosis.

The research team concluded that perf-DCs most likely represent a regulatory cell subpopulation that plays a key role in protecting the body from developing metabolic syndrome and autoimmunity. The team suggests that it would be interesting to investigate whether patients with multiple sclerosis and other autoimmune diseases indeed lack these regulatory perf-DCs.