Roles of MALT-1 and NFKI-1/IKBzeta in IL-17 neuromodulation

Nerve cells, or neurons, are specialized cells that sense internal and external cues and coordinate animal responses, for example specific behaviors. Neurons interact both with other neurons and with many other cell types in the body, e.g. in the digestive tract to influence feeding, and muscles to regulate movement. There is also important crosstalk between neurons and cells of the immune system. Immune cells form an intricate surveillance system that detects pathogen insults and engages in defensive responses. These immune responses are coordinated by cytokines, small proteins, which act as signals. One such cytokine is called interleukin 17, or IL-17. IL-17 drives inflammation following infection. Interestingly, increased IL-17 levels have recently been shown to impinge on fetal brain function and development when pregnant mice suffer infection, suggesting IL-17 can influence neuron function in ways that are poorly understood. IL-17 is conserved, that is, it is found in many animals. Its function can therefore be studied in animals that are experimentally much more tractable than mice. We recently found that IL-17 also regulates the function of neurons in the small worm C. elegans. Studying C. elegans has proven to be a fast and cheap way to understand basic biological mechanisms, and discoveries made using this animal can usually be translated to mammals. In C. elegans IL-17 increases the activity of a neural circuit that mediates responses to oxygen. I will combine genetics, biochemistry, cell biology and molecular approaches to dissect how IL-17 mediates these effects at a molecular mechanistic level. My work will elucidate molecular mechanisms underlying cytokine-dependent neuronal modulation. Ultimately, such advances can help us understand how immune cells communicate with and shape neuron function. Such interactions are thought to be important in a range of diseases, including for example autism, major depressive illness and neurodegeneration.