The intestine is continually exposed to viruses, bacteria and parasites which threaten its function and against which we must defend ourselves. This is the role of the protective immune response and to combat infection, the intestine contains parts of the immune system. However, the majority of the food we eat is also ?foreign? to our immune system, as are the huge numbers of harmless bacteria (commensals) that live normally in our intestines and are essential for life. It is important that we do not attempt to make protective immune responses against these useful materials, as this can lead to severe intestinal disorders such as coeliac disease and Crohn?s disease. Indeed, the immune system normally becomes unresponsive (tolerant) to these materials as it has evolved mechanisms for distinguishing between dangerous and harmless materials. It is important to understand how this happens, not only to have a better chance of treating intestinal disease, but also because there is a great need for new vaccines to combat infections of the intestine. In addition, it may be possible to treat a number of inflammatory conditions such as diabetes and rheumatoid arthritis by exploiting this ability of immune system to become tolerant to ingested materials. A considerable amount is already known about the cellular processes involved and it now seems clear that the signals dictating how a particular population of T lymphocytes (those carrying the CD4 marker) responds may be very different in cells reacting to dangerous versus harmless materials. Thus, it may be possible to target some of these signals to deliberately switch on or off immune responses in the intestine. However, progress in this area has been limited by the fact that it is extremely difficult to identify directly those CD4+ T cells that respond. Moreover, study of the signals usually requires cells to be removed from the immune system and submitted to harsh biochemical processes. We have now developed new models that allow normal and mutant antigen specific T lymphocytes to be tracked and characterised in the intact immune system with highly sensitive laser-driven microscopy techniques that can assess such signals in individual cells. By analysing these events in situ, we hope to be able to identify precisely molecules that might prove useful in treatment of disease and in vaccine development.

The intestine has a surface area nearly two hundred times greater than the skin, and is exposed to many pathogenic micro-organisms. It requires an effective immune response to protect it from infections. On the other hand, immune responses must not be made against the harmless bacteria and food proteins that are also present. When they occur, these inappropriate responses have serious consequences, leading to inflammatory bowel diseases or food allergies. To ensure our health, the balance between ?immunity? and ?tolerance? must be maintained. A critical cell for maintaining this balance is the dendritic cell (DC). DCs migrate continually, in lymph, carrying information about the intestine to the immune cells in the mesenteric lymph nodes (MLN). On reaching the MLN, DCs interact with T lymphocytes. This interaction is thought to control whether immunity or tolerance will occur. Understanding how DCs control these processes is likely to be highly beneficial in the design of oral vaccines or prevention of inflammatory bowel diseases. However, study of migrating DCs has been difficult because they cannot easily be separated from other cells in the MLNs. The only way to collect cells which are certain to be migrating DCs is by surgery, which is used to collect the DC-containing lymph. Previously this surgery has only been possible in large animals. We have developed humane surgical techniques to collect migrating DCs from mice, and to return them to the MLNs. This will enable us, for the first time, to study these cells and their interactions with T cells, using the sophisticated immunological techniques and resources that are only available in mice. We are currently the only group in the world able to collect migrating DCs from mouse lymph. We believe that the study of these cells will generate important information about how immune responses are controlled.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Cyber- and motion sickness are debilitating for many people, limiting both travel opportunities, and the use of new technologies such as virtual and augmented reality. These forms of sickness are due to nauseogenic sensory mismatch (NSM). Cybersickness affects up to 50% of people use who AR and VR headsets. Motion sickness affects 30% of travellers in all forms of transport, with even more getting sick if they use AR or VR as a passenger. To mitigate the effects of NSM, the PhotoMod project will demonstrate the efficacy of a novel transcranial photobiomodulation (tPBM) technique using near-infrared light. This is delivered by LEDs on the scalp shining invisible light into the brain, focused on the human vestibular network (HVN) to create neural entrainment. Our novel method extends work on the ERC ViAjeRo project which used transcranial alternating current stimulation to create entrainment in the HVN. We use this to synchronize the phase information of endogenous neural oscillations associated with NSM in the HVN to an external phase stimulus generated by tACS, which mirrors healthy phase information. We have found very significant benefits for NSM with this method. However, tACS has many drawbacks for commercial application. tPBM overcomes all of these as it is: more precise, safer, more comfortable and cheaper. In PhotoMod, we will develop new hardware and software to deliver tPBM in a commercial form, then test it as a mitigation for cybersickness at home and for motion sickness on the road. The final result will be a commercialisable wearable system that can mitigate the effects of cyber and motion sickness across a wide area of applications.