Molecular Modulator of Regulatory T-Cell Behavior Identified

A mechanism has been identified that explains how regulatory T-cells (Treg cells) suppress harmful T-cell responses that can lead to the development of autoimmune diseases such as type I diabetes and rheumatoid arthritis.

Treg cells play a pivotal role in suppressing self-harmful T-cell responses, but how they mediate suppression to maintain immune homeostasis and limit responses during inflammation has not been well understood.

Investigators at the University of Manchester (United Kingdom) examined the role of the integrin alphavbeta8 in the modulation of Treg behavior. They reported in the May 12, 2015, online edition of the journal Immunity that effector Treg cells expressed high amounts of integrin alphavbeta8, which enabled them to activate latent transforming growth factor-beta (TGF-beta).

Working with a mouse model, the investigators showed that specific deletion of integrin alphavbeta8 from Treg cells did not result in the generation of spontaneous inflammatory or autoimmune behavior, suggesting that this pathway was not important in Treg cell-mediated maintenance of immune homeostasis. However, Treg cells lacking expression of integrin alphavbeta8 were unable to suppress pathogenic T-cell responses during active inflammation.

Senior author Dr. Mark Travis, lecturer in inflammation research at the University of Manchester, said, “Regulatory T-cells are already being used in clinical trials where the cells are taken from the patient, multiplied, and then given back to the patient to suppress their illness. By understanding the mechanisms behind how regulatory T- cells work, we could improve on these therapies, which can be potentially useful in conditions ranging from type I diabetes to multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease. This knowledge is vitally important when trying to make regulatory T-cells for therapy. By knowing the importance of this pathway, we can now work to improve the suppressive nature of regulatory T-cells to make them more effective as treatments for disease.”

“It is fascinating that getting rid of just one molecule can have such an impact on the body’s ability to fight disease. Our research is all about how the molecules interlink and react to each other, and in certain situations targeting just one molecule can boost or inhibit a response, said Dr. Travis.”

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