Welcome to the next installment of our regular update where we report on research from the world of immunology, highlighting work from BSI members that has hit the headlines over the past few weeks.
Molecules behind immune ageing identified
Is it possible to reverse immune system decline associated with ageing? That’s the question asked by researchers from University College London and Oxford University who study the molecular processes behind how our immune system ages. For this paper, published in Nature Immunology, they focused on a group of molecules called MAPKs (mitogen-activated protein kinases). These molecules act as a brake on T lymphocytes, stopping them from performing certain functions, and are activated via signals that sense low nutrient levels or those related to the ageing process.
The researchers found that sestrins (an inhibitory protein molecule) can bind to and co-ordinate simultaneous activation of several types of MAPKs in T lymphocytes within a new immune-inhibitory complex (termed sestrin-MAPK activation complex, or sMAC). T cells from older people or mice were more likely to form a sMAC, but disrupting this complex could enhance vaccine responsiveness in old mice.
“MAPK pathways have been studied for nearly thirty years. The discovery of the sMAC illuminates a very different mode of MAPK activation, introducing the possibility of new forms of immunotherapy. How the sMAC feeds into metabolic and pathophysiological processes will be important to examine in the future,” said author and BSI member, Dr Alessio Lanna from UCL Infection & Immunity and Nuffield Department of Medicine, Oxford University.
BSI member Arne Akbar from UCL added: “We’re on the cusp of boosting immunity in old animals, and possibly in old humans as well. It’s now essential we identify safe ways to counteract some of these deleterious changes in the immune system during ageing.”
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Read the full article: Lanna et al. 2017 Nature Immunology doi:10.1038/ni.3665
Immune benefits to chewing your food
We know relatively little about the complexities of how the immune system acts in the mouth to prevent infection. However, a new study from researchers at the University of Manchester and the National Institutes of Health in the USA has shed more light on this topic, in particular what happens when we chew our food.
From studies on both mice and humans, they report that the action of chewing (and the damage that this causes to the gums) stimulates the production of a key type of immune cell, the T helper 17 (Th17) cell, which is important in protecting against bacterial and fungal infections.
Lead author and BSI member Dr Joanne Konkel, from The University of Manchester, said: “The immune system performs a remarkable balancing act at barrier sites such as the skin, mouth and gut by fighting off harmful pathogens while tolerating the presence of normal friendly bacteria. Our research shows that, unlike at other barriers, the mouth has a different way of stimulating Th17 cells: not by bacteria but by mastication. Therefore, mastication can induce a protective immune response in our gums.” The work was published in the journal, Immunity.
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Read the full article: Dutzan et al. 2017 Immunity doi: 10.1016/j.immuni.2016.12.010
Intestinal immunity regulated by feedback control of AhR signalling
A new study published in Nature reports on the actions of a protein called Cyp1a1 that may assist the immune system in fighting off intestinal pathogens. We already know that the aryl hydrocarbon receptor (AhR) protein works at barrier sites in the body such as the skin, gut and lungs to protect against damage from external influences, for example pathogens. Through studying AhR in the guts of mice, scientists at the Francis Crick Institute led by BSI member Professor Gitta Stockinger, have discovered that Cyp1a1 appears to regulate AhR activity. It does this by degrading AhR activation molecules (called AhR ligands) decreasing AhR signalling through a feedback mechanism.
“Molecules that activate AhR can come from our diet, but also from our intestinal bacteria,” said Professor Gitta Stockinger. “Activation of AhR turns on enzymes such as Cyp1a1. Normally the function of these enzymes is to degrade the molecules that originally activated AhR and turn it back off."
The researchers found that mice who had overactive Cyp1a1 had lower AhR ligand levels, which led to a decreased number of the immune cells that depend on these ligands. When challenged with Citrobacter infection, these mice were unable to fight off the infection, although increasing certain dietary nutrients (particularly those found in cruciferous vegetables) helped to control the increased Cyp1a1 activity.
“As indicated in our study, it is entirely conceivable that some people have mutant Cyp1a1 enzymes that have abnormally high activity,” said Professor Stockinger. “In humans, this could play a role in inflammatory intestinal diseases where people with genetically determined overactive Cyp1a1 would be particularly sensitive to infections.”
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Read the full article: Schiering et al. 2017 Nature doi: 10.1038/nature21080