11 April 2018

Scientists have made an important discovery into the genetic basis of chronic graft-versus-host disease following bone marrow transplant.

Dr Xue-Zhong Yu and colleagues at the Medical University of South Carolina, USA, found that T-cell and B-cell changes that cause chronic graft-versus-host disease (cGvHD) are linked to the activity of microRNA family miR-17-92.

MicroRNAs are small regulatory stretches of RNA that do not code for protein as most RNAs do, but instead regulate the expression of other genes.

Dr Yu said: "It's been a big challenge to try to find a target for cGVHD therapies, because of the more complex immune reaction in cGVHD and the fact that its cellular and molecular mechanisms are not as well understood."

The team had previously discovered that, in acute GVHD, miR-17-92 is crucial in regulating CD4 T-cell proliferation and differentiation. This new work confirms that miR-17-92 also regulates T- and B-cell differentiation and function in the development of cGVHD.

Full details appeared in the journal Blood on Monday (2 April).

Co-author Dr Yongxia Wu reports: "The mechanism for how miR-17-92 regulates T- and B-cells was very consistent. We also found that blocking miR-17 substantially reduced cGVHD symptoms in mice.

"That's exciting because it provides strong evidence that this miR may be a good target for controlling cGVHD after allogeneic bone marrow transplant."

The team add that cGVHD has a similar pathophysiology to some autoimmune diseases, so these findings could be useful for new treatments and preventive therapies in other conditions.

Source: Wu, Yongxia, et al. "MicroRNA-17-92 is required for T-cell and B-cell pathogenicity in chronic graft-versus-host disease in mice." Blood (2018): blood-2017.

Link: https://doi.org/10.1182/blood-2017-06-789321


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