New findings open up autoimmune disease treatment options

By Wai Lang Chu

- Last updated on GMT

Related tags: Cells, Immune system

A new finding has the potential to pave the way for better
treatment options for autoimmune diseases as researchers discover a
signalling molecule can yield a rapid, inexpensive way to make
large numbers of immune cells.

The ability to easily make large numbers of these cells opens the door to improved treatment and a better understanding of autoimmune diseases such as type1 diabetes and arthritis.

Autoimmune diseases occur as a result of the failure of an organism to recognise its own constituent parts (down to the sub-molecular levels) as "Self," which results in an immune response against its own cells and tissues.

Any disease that results from such an aberrant immune response is termed an autoimmune disease, the prominent examples being Systemic Lupus Erythematosus (SLE), Sjögren's syndrome and Rheumatoid Arthritis (RA).

Researchers discovered that the signalling molecule has an unusual affinity for alcohol.

It's a lethal choice for the signalling molecule that, in turn, also kills T cells that need the enzyme phospholipase D to survive. Previously, it was unknown whether regulatory T cells required the molecule.

"What we have found is that if you block this enzyme, almost all T cells die after three days but the regulatory T cells can survive,"​ said Makio Iwashima, MCG immunologist and the study's corresponding author.

"After three days, we give them some food to grow and, in one week, you get about 90 per cent pure regulatory cells."

T cells are components of the immune system designed to attack invaders such as bacteria and viruses; regulatory T cells are a small subset that prevents the cells from also attacking body tissue.

The approach worked with laboratory-grade alcohol, called butanol, as well as beverage-grade ethanol.

"Normally, regulatory T cells constitute about 2-5 per cent of all T cells,"​ Iwashima said. "Isolating them is doable but a long, expensive process."

When researchers gave some of the regulatory T cells to a mouse model of inflammatory bowel disease, the symptoms, including dramatic weight loss, went away.

Animals showed no classic signs of inflammation, just a significant increase in regulatory cells.

"Our prediction and our hope is that we can restore balance,"​ said Iwashima. "The usual 5-95 per cent ratio of regulatory cells to non-regulatory T cells is lost in those with autoimmune disease,"​ he added.

However, too many regulatory cells also can be a problem, he says, noting that cancer patients have higher levels of regulatory cells.

Regulatory T cell therapy also resolved symptoms in a model of graft versus host disease, a problem for some bone marrow transplant patients when immune cells from the donor start attacking.

This finding indicates a potential role for helping transplant patients keep new organs, the researchers say.

Iwashima and his colleagues believe the best way to optimise cell percentages is to do what the body does. In fact, they already are searching for an endogenous substance that interferes with phospholipase D.

"Ultimately, that is the most natural way, if we can find the compound in our bodies that can do the job,"​ Iwashima said. He theorises that this natural substance helps destroy non-regulatory T cells when the body gets too many, say after fighting a big infection, and that it may not work well enough in people with autoimmune disease.

Related topics: Preclinical Research

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