Researchers identify immune cells that fight obesity in animal model.


The intriguing relationship between metabolism and the immune system has been receiving increasing attention over the past few years.  It is known that macrophages accumulate in adipose tissue during obesity. Recent findings also demonstrate a role for other immune cell subsets, including T cells, B cells, eosinophils, and neutrophils, in the control of fat tissue inflammation.
This heightened immune response in obesity changes the types and amounts of lipids and adipokines released from adipose tissue, which can then negatively impact other tissues and promote metabolic disease. Increased adipose tissue inflammation is now considered one of the primary drivers of insulin resistance associated with obesity. Therefore, the immune system is now at the forefront of metabolic research focused on determining mechanisms by which immune cells accumulate in obese adipose tissue.  Now, a study from researchers at the Weizmann Institute has identified another small subtype of immune cell that appears to prevent metabolic syndrome, obesity, high blood pressure, and high levels of blood sugar and cholesterol.  The opensource study is published in the journal Immunity.

Previous studies have shown that obesity increases the number of chemokines and chemokine receptors in fat tissue.  Research has identified various immune cells as metabolic controllers with pathogenic or regulatory potential.  Three T lymphocyte subsets might play distinct roles in adipose tissue immune homeostasis.  In particular, the infiltration of CD8+ T cells to the adipose tissue has been shown to precede macrophage influx into the obese fat tissues and CD8+ T cells are involved in macrophage recruitment in obesity. With studies showing that the immune system plays a role in obesity, the lab state that it should be noted that the majority of these studies were performed on mice deliberately fed a high-fat diet. The current study was performed on mice fed a regular diet; with results showing that immunological mechanisms can play a role in obesity and metabolic syndrome without any connection to dietary fat.

The current study focused on dendritic cells, with the emphasis on a rare subtype of dendritic cells possessing a killing protein called perforin that enables them to eliminate other cells on demand. To reveal the function of these cells in the body, the lab used mice that lacked perforin-rich dendritic cells.  Results show that these mice became overweight and then developed symptoms of metabolic syndrome.  Data findings show that fat tissue had abnormally high levels of inflammation-causing immune T cells.

Results show that when these cells were removed from the fat tissue of the mice lacking perforin-rich dendritic cells, the mice did not grow obese.  The researchers conclude that these findings suggest that perforin-rich dendritic cells regulate the levels of certain T cells, and by keeping these T cells in check, they apparently prevent metabolic syndrome.

The team surmise that in addition to providing new insights into metabolic syndrome, the study may also shed new light on autoimmunity as the mice lacking perforin-rich dendritic cells were more prone than usual to develop an autoimmune disease equivalent to multiple sclerosis in humans.  For the future, the researchers state that it now remains to be investigated whether patients with autoimmune disease lack these regulatory cells.

Source: Weizmann Institute

 

Fat tissue cells are enlarged and more loosely packed in mice lacking perforin-rich dendritic cells (left) compared with the fat tissue of regular mice (right). Inset: crown-like structures within the fat tissue (left, dark brown) are associated with increased inflammation.  Perforin-Positive Dendritic Cells Exhibit an Immuno-regulatory Role in Metabolic Syndrome and Autoimmunity.  Reisner et al 2015.

Fat tissue cells are enlarged and more loosely packed in mice lacking perforin-rich dendritic cells (left) compared with the fat tissue of regular mice (right). Inset: crown-like structures within the fat tissue (left, dark brown) are associated with increased inflammation. Perforin-Positive Dendritic Cells Exhibit an Immuno-regulatory Role in Metabolic Syndrome and Autoimmunity. Reisner et al 2015.

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