Project 459015

Innate lymphoid cells (ILCs) are a rare population of immune cells that are the first line of defence against viruses, bacteria, and parasites. Type 2 ILCs (ILC2s) are type of ILC found in the lungs, gut, and skin. These cells are important for lung tissue repair after viral infections and fighting parasitic worm infections in the gut and lungs. On the other hand, ILC2s can also cause adverse effects such as increasing inflammation during airway allergic responses and asthma. How these immune cells arise and function is not fully understood. It is believed that all ILCs develop in the fetal liver and adult bone marrow from immature cells and undergo several maturation steps that involve different sets of DNA regulators. These DNA regulators determine which ILC type the precursor cell will develop into. DNA regulator "GATA3" is the most important for ILC2 development and it helps ILC2s express the receptor for an essential immune hormone, "interleukin-7" (IL-7). Our lab has found that IL-7 is an important factor for ILC2 development. Disruption of the IL-7 receptor decreases both the number of ILC2s present and the level of GATA3 they express, while treating cells with IL-7 causes the opposite effect, with more ILC2s and higher GATA3 expression. We want to test whether IL-7 controls ILC2 development through different DNA regulators. This project will identify the genes and proteins controlled by IL-7 in fetal liver ILC2s using gene sequencing techniques. We will also examine if stimulating the genes and/or proteins controlled by IL-7 in ILC2 development can reverse the effects seen when IL-7 receptor is disrupted. This study will increase our understanding of a rare but vital cell population and help in the development of new therapies for immune diseases and infections.