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Immunology Update - August 2016

Welcome to the next installment of our regular monthly slot where we report on research from the world of immunology, highlighting work from BSI members that has hit the headlines over the past four weeks.

Potential mechanism to reboot immune system after bone marrow transplant

The populations of some immune cell types, in particular T cells, are slow to recover following bone marrow transplant, but the reason for this is not known.  Using murine models, researchers at the University of Birmingham have discovered a new in vivo mechanism involving the thymus that could help to explain this phenomenon.

A ViSNE plot of immature T-cells in the thymus.

A ViSNE plot of immature T-cells in the thymus. Highlighted in red is a population of T-cell progenitors that colonise the thymus and give rise to all T-cells.

They found that Lymphotoxin β receptor, a cell surface molecule, controls the entry of T-cell progenitors to the thymus, both in a healthy state and during immune recovery following bone-marrow transplantation. Importantly, the team also found that, in mice, antibody-mediated stimulation of this receptor following a bone marrow transplant increased the number of donor-derived T-cells and boosted initial thymus recovery.

Writing in Journal of Immunology, lead author and BSI member, Professor Graham Anderson explains, “Post-transplantation, T-cell progenitors derived from the bone marrow transplant can struggle to enter the thymus, as if the doorway to the thymus is closed. Identifying molecular regulators that can ‘prop open’ the door and allow these cells to enter and mature, could well be a means to help reboot the immune system.” The team now hope to expand their studies to see if the same molecular mechanism functions in humans.

Read the press release

Read the full article: Lucas et al. 2016 Journal of Immunologydoi:10.4049/jimmunol.1601189

What scales the T-cell response?

T LymphocyteOne question that has baffled immunologists is how the immune system manages to proportionally scale its response in relation to any threat it encounters. In this thought-provoking article, published in Trends in Immunology, Professor Michael Dustin and Dr Viveka Mayya from the University of Oxford set out their hypothesis for how this occurs.

BSI member Professor Michael Dustin, explains, “While an overwhelming T-cell response might on the face of it sound effective, it brings risks of immunopathology, where an over-active immune system destroys healthy human tissue, not just the invading disease-causing pathogen.  Scaling the immune response is therefore a safer option, and we know that is what happens. Until now, however, no one had suggested how the body does that.”

They hypothesise that the scale of the T-cell response to an infection could be mediated through their interactions with dendritic cells. Several studies have shown that T-cells slow down and accumulate around dendritic cells when an infection is severe, i.e. their interaction length is prolonged.  The authors discuss the reasons why they think this interaction length may be the key factor in determining immune response severity.

Read the press release

Read the full article: Mayya & Dustin 2016 Trends in Immunology 37 513–522 doi:

New therapeutic target for autoimmune diseases

New research, published in Scientific Reports, has discovered a potential novel strategy to treat a variety of autoimmune diseases, such as multiple sclerosis or psoriasis. Dimethyl fumarate is a drug that is known to be effective against a variety of autoimmune diseases because of its anti-inflammatory properties.  However, its molecular target and mode of action were not known until now.

Through a combination of in vitro and in vivo studies, researchers from the University of Dundee led by BSI member Dr Simon Arthur found that dimethyl fumarate targets the actions of a particular group of enzymes in the body called E2s, some members of which are active in inducing inflammation. “This suggests that more selective inhibitors of E2s may be well tolerated and validates these enzymes as targets for future drug development,” commented Dr Arthur.

Read the press release

Read the full article: McGuire et al. 2016 Scientific Reports doi:10.1038/srep31159

Image credits: ViSNE plot of immature T-cells in the thymus – University of Birmingham; T lymphocyte – NIAID