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06 November 2017

Researchers have identified a gene that may help provide protection against graft-versus-host disease (GvHD).

The finding has come from a study of the role of the protein tumour necrosis factor alpha, or TNF alpha, in inflammatory diseases.

This involved a study of the ATG16L1 gene, which the researchers now say could be used to protect against GvDH if it can be stimulated.

Dr Ken Cadwell of at NYU School of Medicine, New York, USA, and colleagues explain that TNF alpha encourages immune cells to gather at the site of an infection in order to destroy foreign invaders - but the protein can also mistakenly target the body's own cells, leading to autoimmune disease.

The team carried out lab experiments with mice where they altered Paneth cells, which normally protect the gut from microbes. The Paneth cells were engineered to lack a functional ATG16L1 gene.

These cells were found to be five times more likely than normal cells to die when TNF alpha signals are active. The findings indicate that the action of ATG16L1 normally prevents TNF alpha-driven inflammation from destroying too many Paneth cells.

Further tests on rodents indicated that the ATG16L1 gene also appears to protect tissue against the spikes in TNF-alpha levels seen in graft-versus-host disease.

Dr Cadwell says: "Our study results are the first to argue that we may be able to treat inflammatory bowel disease and protect against transplant rejection not only by blocking TNF alpha as is done currently, but also by stimulating ATG16L1 to prevent early death of cells lining the gut."

Source: The Journal of Experimental Medicine

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