Researchers link diabetes with Sjogren’s syndrome

Sjögren's syndrome is an autoimmune disease where the body’s own immune system attacks the exocrine glands that produce tears and saliva.

Sufferers experience dryness that can be irritating and can also lead to fatigue and depression. Sjögren’s syndrome affects as many as 100,000 Australians, mainly women over the age of 50.

Type 1 diabetes is also an autoimmune disease, except it attacks insulin-producing cells in the pancreas.

Now researchers at the Garvan Institute in Sydney have identified a unique immune cell that is associated with Sjögren’s syndrome, and which also appears to be involved with type 1 diabetes.

The cell is a sub-class of CD4⁺ T helper cells, dubbed TCCR9 cells. They are uniquely distinguished by their co-expression of interleukin-21 and a cell surface receptor that is switched on when cells migrate through the gut, CCR9.

Although TCCR9 Th cells were observed in healthy mice and humans, they were enriched in the inflamed pancreas and salivary glands of NOD mice and in the circulation of Sjögren’s syndrome patients.

Co-authors Dr Cecile King and PhD student Helen McGuire found that TCCR9 cells were present in healthy mice and humans, but they were found in particularly high concentrations in the inflamed pancreas and salivary glands of mice with diabetes, and in the circulatory system of Sjögren’s syndrome patients.

This suggests the TCCR9 cells may be responsible for attacking the pancreas or exocrine glands, thus leading to type 1 diabetes or Sjögren’s syndrome respectively.

The authors also collaborated with Associate Professor David Fulcher from Sydney’s Westmead Hospital, who found very high levels of these same cells in patients with Sjögren’s syndrome.

This finding may shed insight into both diseases, and suggest possible avenues for treatment.

“We know from our research in mice that if you target these cells, you can completely prevent immune mediated destruction of the salivary glands and pancreas,” said Dr King.

“In other words, you can prevent mice that are genetically programmed to develop Sjögren’s syndrome and Type 1 diabetes from ever developing those diseases.

“You find these cells in the gut, but there are very few of them in other parts of the body of a healthy person. When the body shifts into disease mode, TCCR9 cells are activated in the gut, and then disseminate to the accessory organs of the digestive system – the pancreas and salivary glands. Exactly what triggers that process remains unclear.”

“When we looked at 15 patients with Sjögren’s syndrome, we found there was a fivefold increase of these cells in their blood. While very interesting, we would need to analyse a much larger cohort for this figure to signify a general trend. “So we intend to extend our study of patients with Sjögren’s syndrome, as well as establish whether or not there are similarly expanded populations of these cells in people with Type 1 diabetes. This will determine whether these cells could become a biomarker of disease as well as a therapeutic target for patients with both with Type 1 diabetes and Sjögren’s syndrome.”

The paper was published today in the journal Immunity.