iNKT cells as drivers for preterm labour

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The purpose of this work is to develop treatments to prevent preterm birth. Preterm birth is a big health problem. Globally, over 1 million children die each year from the complications of preterm birth. In the UK around 55,000 babies (around 7.8% of all UK births) are born preterm. Despite much effort, these rates are rising. Although survival rates are improving, with 77% of UK babies born at 26 weeks gestation now leaving hospital, survivors are at increased risk of short term morbidity and long term disability. Long term disability includes respiratory problems, motor and sensory impairment, learning difficulties, and social and behavioral difficulties and is driven not only by the consequences of prematurity, but by the intrauterine inflammation which precedes prematurity. Together the complications of preterm birth result in a £2.946 billion estimated annual costs of preterm birth to the public purse in England and Wales (2006 prices). Unfortunately, there are hardly any treatments in development for preterm birth. Even if we use all the treatments we currently have for all women at risk, preterm birth rates will only fall by 0.2% in the UK i.e., from 7.8% to 7.6%. We and others have suggested that this lack of good treatments, and the lack of treatments in development is because we don't properly understand what causes women to go into preterm labour, nor do we understand what triggers labour at term.We and others have shown that "inflammation" is key to the start of labour, both at term and preterm. We have tried several strategies to treat inflammation and hence prevent preterm labour, but none has yet been effective. We think this is because we are trying to stop inflammation well after it has started. We are now going to look at some immune cells which are involved in the start of the inflammatory process and which have been shown to be important in stimulating preterm labour in a mouse model. These cells (invariant [i] NKT cells) are important because they link two halves of the immune system, and because they can respond rapidly to "danger" signals, including those present in pregnant women.In this study we are going to look at these cells in the place that we think that labour starts - the lining of the womb which separates mother from baby. We will see what happens in the lining of the womb in labour, and then look at how the iNKT cells change in the lining of the womb in labour. We will see if we can start labour in a mouse model by stimulating these iNKT cells, and then see if drugs which prevent iNKT activation can prevent inflammation induced preterm labour. Next, we will look to see if these iNKT cells are activated early in the process of labour - we think they will be. Lastly, we will see how progesterone, which is currently used to treat preterm labour in some women, might affect iNKT cells.We believe our work will generate new understanding of how labour starts, and so ultimately develop treatments to prevent preterm labour. Such treatments could make major inroads into preventing the deaths of up to 1 million children per year.