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Immunology Update - June 2017

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.

Different protein subtypes can influence the immune response

Researchers at University of Birmingham have identified a small genetic variation that could be having a big impact on our immune response.

The study, published in Science Signalling, focuses on the immune protein ULBP6, which activates Natural Killer (NK) cells by binding to the receptor NKG2B and triggering the removal of the damaged target cell. There are two subtypes of the ULBP6 protein, which can be found in different people. The researchers showed that although the subtypes only differed by two amino acids, this change had a great impact on the protein’s function. They found that one of the ULBP6 subtypes binds more strongly with the receptor which impaired activation of NK cells.

Author and BSI member Prof Ben Willcox said, "The 'sticky' form of ULBP6 binds over 10 times more strongly to NKG2D but a major surprise was that this acted to reduce killing by the immune system rather than increase it.” He adds, "We now want to understand how this information might be used to improve the outcome of patients undergoing stem cell transplantation."

These findings could explain why inheriting a certain ULBP6 subtype causes some patients to have a poorer outcome after stem cell transplantation. 

Read the press release here

Read the full article: Zuo et al. 2017, Science Signalling doi: 10.1126/scisignal.aai8904

Changes in cell type can determine the outcome of infection

The severity of an infection is dependent on the balance between immune suppressive and immune boosting white blood cells. A recent study, by researchers at the Francis Crick Institute, has shown that the conversion of immune suppressive to immune boosting cells could be disrupting this balance and enhancing immunity.

The researchers infected mice with an intestinal worm and monitored the fate of white blood cells using a fate-reporter system. The results from the study, published in the Journal of Experimental Medicine, showed that a significant proportion of immune suppressive cells had converted to an immune boosting fate, which helped the mice fight off the infection. Additionally, the researchers also discovered a high proportion of conversion in the lungs of mice with induced airway allergies, which could be worsening the symptoms of asthma. 

“The conversion of immune-suppressing cells to immune-boosting cells is beneficial for providing immunity against intestinal worms, but can make allergies worse," said lead author and BSI member Dr Victoria Pelly. "If we can find a way to target this mechanism, it will be extremely useful in the clinic."

However, the molecular mechanisms underlying these conversions are likely to be different for asthma and worm infection. 

Read the press release here

 Read the full article: Pelly et al. 2017, Journal of Experimental Medicine doi: 10.1084/jem.20161104

RNA binding proteins help immune cells maintain their identity   

The immune system comprises of multiple cell types that need to maintain their cellular identity in order to function correctly. A team of researchers at the Babraham Institute in Cambridge, in collaboration with researchers at the University of Birmingham, have discovered how the RNA binding protein, ZFP36L, maintains the identity of marginal zone B cells (MZ B cells).  MZ B cells play a pivotal role in early detection of infection by screening the blood for pathogens as it enters the spleen, and loss of these cells greatly increases susceptibility to disease.

Senior author and BSI Congress committee member Dr Martin Turner said, “Our immune system contains many different types of cells with unique roles. Extremely complex processes govern the development and function of each of these cell types. This study adds to our understanding of the multi-level control over cellular identity for cells in the immune system.”

The study, published in Nature Immunology, shows that ZFP36L, promotes the proper location and function of MZ B cells, by blocking the production of certain proteins that would cause the cell identity to change.

Lead author and BSI Forum committee member Dr Rebecca Newman said, “ZFP36L1 plays an important role in MZ B cells by controlling the levels of mRNA from genes such as IRF8 and KLF2. If ZFP36L1 is lost, MZ B cells leave the marginal zone of the spleen and many of them die.”

Read the press release here

Read the full article: Newman et al. 2017, Nature Immunology doi: 10.1038/ni.3724