Obesity isn’t just a matter of “bad genes” or unhealthy lifestyles. It also involves immunological mechanisms. In fact, certain immune cells appear to influence fat tissue, controlling the storage and release of energy. Fat cells also produce inflammatory molecules that can disrupt the immune system.

While the intricate relationship between the immune system and fat tissue is but partially understood, many scientists already suspect that obesity is an autoimmune, inflammatory disorder. Additional evidence in support of this line of thinking has been presented by scientists from the Weizmann Institute. They say that the lack of a particular type of immune cell caused mice to gain excess weight and develop metabolic abnormalities.

As might be expected, the mice gained weight more quickly if they were fed a high-fat diet. More surprisingly, the mice still gained weight even if they were fed a standard diet.

These results appeared September 15 in the journal Immunity, in an article entitled, “Perforin-Positive Dendritic Cells Exhibit an Immuno-regulatory Role in Metabolic Syndrome and Autoimmunity.” As the title indicates, the immune cells of interest were perforin-expressing dentritic cells (perf-DCs). Perf-DCs represent a relatively rare subpopulation of immune cells. Yet they appear to play an important role in maintaining a balanced collection of T immune cells in fat tissue.

The Weizmann Institute scientists, led by Yair Reisner, Ph.D., used bone marrow transplantation to generate animals selectively lacking perf-DCs. These chimeras, the scientists reported, progressively gained weight and exhibited features of metabolic syndrome.

“This phenotype was associated with an altered repertoire of T cells residing in adipose tissue and could be completely prevented by T cell depletion in vivo,” the authors of the Immunity study wrote. “A similar impact of perf-DCs on inflammatory T cells was also found in a well-defined model of multiple sclerosis, experimental autoimmune encephalomyelitis.”

These combined observations suggest that one function of these perforin-expressing dendritic cells is to remove potentially autoimmune T cells, and in so doing, decrease inflammation. While the connection between fat cells and inflammation has already been shown in mice fed a high-fat diet, this is the first time that researchers have demonstrated the connection in animals on a regular diet, simply by eliminating perforin-expressing dendritic cells.

Perforin-expressing dendritic cells may be critical for protecting against metabolic syndrome and autoimmunity, and shifting the abundance of these cells in relation to other immune cell populations may help prevent or treat such conditions.

“Notably, mice lacking these regulatory dendritic cells were also found to be more prone to develop another form of autoimmunity with symptoms similar to those found in multiple sclerosis,” said Dr. Reisner. “It is hard to predict how this might impact patient care, but we should initially try to find if the absence of this rare subpopulation of cells is associated with obesity, metabolic syndrome, or any autoimmune or other immune abnormalities.”