Beefing up a protective cell to tackle diabetes and obesity

7 Dec 2015

Prof Lydia Lynch has secured ERC funding to look at how immune cells can tackle obesity and diabetes.

Obesity and diabetes have strong links with the immune system, so wouldn’t it be great if we could harness our own immune systems to tackle them? Dubliner Prof Lydia Lynch is all set to do this: by beefing up a protective immune cell.

Obesity and type 2 diabetes are closely linked through chronic inflammation, but ramping up naturally occurring ‘invariant natural killer T’ (iNKT) cells seems to redress the balance in mice. The mice lose fat and their diabetes is less severe, and Lynch wants to know why.

Now based in Harvard, she will move to Trinity College Dublin next summer to start a five-year project funded by the European Research Council to the tune of just over €1.8m. She will look at how particular lipids (fats) could manipulate the immune system, and iNKT cells in particular, to prevent or treat obesity and type 2 diabetes.

Protective immune cells

It all started several years ago, when Lynch was working in University College Dublin (UCD) and St Vincent’s Hospital with obesity expert Prof Donal O’Shea and immunology expert Prof Cliona O’Farrelly.

“We found that iNKT cells, which were thought to be very rare in humans compared to mice, were actually not rare, that they were found in adipose tissue or the fat tissue,” explains Lynch.

Lynch found that iNKT cells were turning up in large numbers in the belly fat of lean people, but there were fewer of these cells in the fat of obese people. “Because the iNKT cells were so enriched there we thought maybe they have an important role there,” she says.

Thanks to a L’Oreal-UNESCO International Fellowship, followed by a Marie Curie Fellowship, Lynch went to Harvard Medical School in Boston to study these curious cells, ultimately setting up her own lab there.

Prof Lydia Lynch

Prof Lydia Lynch

Her research has found that mice that genetically lacked iNKT cells became more obese and had more severe diabetes than those with iNKT cells. She also saw that a particular type of lipid activated iNKT cells and reduced both obesity and diabetes in mice. And there was more: in fat tissue, the iNKT cells lose their killer instinct and instead act as anti-inflammatory agents.

“The problem is, when humans and mice become obese, the iNKT cells die and you don’t have these protective cells any more,” she explains. “So the goal is to find out why these cells are dying, and to prevent them dying or to activate them again in obesity.”

Lynch’s work in Trinity will explore this process, and explore other lipids that may be even better suited to the job of boosting iNKT cells to tackle diabetes and obesity in humans.

Obesity and smoking: double immune whammy

It’s not the first time Lynch has described the strong links between obesity and immune function. While working in the lab at UCD, she discovered that obesity and smoking hampered another type of immune cell – the natural killer cells that normally help us to fight off viruses and protect against cancer.

“These natural killer cells are our first line of defence against cancer and viruses, and in obesity you have less of them,” she says. “[In addition,] obesity itself causes them not to work, and so does smoking, so the double hit of smoking and obesity is really bad for them.”

Thrill of discovery

Lynch is enthusiastic about the thrill of discovery when working in science. “I think it’s the best career ever. There is nothing I would rather do than this because it is so exciting every day,” she says.

“There are a lot of highs and lows. Sometimes things don’t work but when they do work it is far better than the lows, and when an experiment works, you have the sense that you are the only person in the world that knows about that, and it is so exciting. If you are a curious person, it is just perfect.”

You can hear a short clip of Lynch talking about the ERC research, ‘Targeting iNKT cell and adipocyte crosstalk for control of metabolism and body weight’, here.

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Overweight man working out image via Shutterstock

Dr Claire O’Connell is a scientist-turned-writer with a PhD in cell biology and a master’s in science communication