Obesity implicated in immune system malfunction, according to animal study

Work carried out here identifies new therapeutic targets to prevent and control obesity-related inflammation and metabolic disease. ©iStock

The links between obesity and the immune system have been outlined by Irish researchers who have identified the impact of diet on immune cells that control inflammation and metabolic function.

Findings from an animal study have pinpointed a type of ‘guardian immune cell,’ or Adipose Type One Innate Lymphoid Cells (AT1-ILCs), located in the fat tissue.

These cells are very responsive to diet and were found to be compromised in obese subjects.

“Fat has its own immune system, which we are only recently learning about,” said Professor Lydia Lynch, associate professor at Trinity College Dublin.

“We have revealed that ILCs keep other immune cells called macrophages in check, by killing them based on certain physiological conditions in the body – they essentially guard against inflammation when macrophages are too numerous in fat. This function is unique as immune cells are not generally supposed to kill other healthy immune cells in non-pathological conditions.”

The findings underlie the role that healthy eating plays in affecting the immune systems.

It has previously been shown that after eating a fatty diet for only five days, ILCs specifically target fat cells. Similarly, their population numbers in blood and fat decrease when weight is lost.

ILC’s protective role

The study took samples of fatty tissue from human and mice subjects to confirm the existence of AT1-ILC numbers.

Mice sharing the same blood circulation were then fed a high-fat diet (HFD) in which the AT1-ILCs exhibited unique behaviour particularly in response to short- and long-term HFD and diet restriction.

At steady state, AT1-ILCs displayed cell toxicity towards these macrophages, specifically called Adipose Tissue Macrophages (ATMs).

Decreased AT1-ILC numbers resulted in changes to inflammatory and anti-inflammatory ATM numbers.

However, as obesity progressed, these macrophages became overwhelmed by the workload and turned inflammatory, which led to more severe obesity and further complications like diabetes.

“We know that macrophages enter fat at the onset of obesity and that they likely do a protective job cleaning up as much excess fat as they can,” said Professor Lynch.

“Importantly, in healthy states, our ILCs protect against this inflammation and metabolic disease by killing the troublesome macrophages in our fat. But when obesity is established these ILCs are depleted and lose their regulatory killing function, which results in a dangerous accumulation of macrophages and all the bad things that come with that.”

Changes in response to weight gain

Fat tissue has been shown to respond to changes in nutrient fluctuations, expanding and contracting to deal with changes in energy intake.

In a lean subject, fat tissue is populated with regulatory cells including iNKT cells and eosinophils.  

However, in a high-fat diet AT1-ILCs rapidly respond to changes in diet, in both human and mice.

iNKT populations have also been found to decrease in human and murine obesity.

“We propose a novel ‘physiological killing’ of macrophages by adipose AT1-ILCs to maintain adipose homeostasis at steady state, highlighting the importance of understanding ILC and macrophage interactions in health and disease,” the study concluded.

 

Source: Immunity

Published online ahead of print: doi.org/10.1016/j.immuni.2017.01.008

“Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity.”

Authors: Lydia Lynch et al.

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