RNAseq_of_UPEC_infected_mouse_bladders

In recent years, a newly defined family of immune cells, the innate lymphoid cells (ILCs) have been identified in a number of tissues, and are enriched at mucosal surfaces and areas that interface with the environment, for example, the gastrointestinal tract (GIT) and skin 3,4. Group 3 ILCs are dependent on RORt for their development and produce IL17A and IL22 in response to IL23 stimulation. In the intestine, ILC3 production of IL22 contributes to the maintenance of epithelial cell health and increases their production of anti-microbial peptides thereby playing a protective role against enteric pathogens 5,6. To date, there are no data that directly address the issue of whether there are ILCs in the renal tract, and if present, the functional significance of these cells in health and disease. Our preliminary analysis of human and mouse tissues show that all three ILC subsets can be found within kidneys and bladder, with ILC3 being particularly prevalent (Figures 1 and 2 - see pdf). We hypothesised that ILC3s contribute to defence against uropathogenic bacteria via production of IL22 and IL17. In keeping with this thesis, IL17-deficient mice have increased susceptibility to pyelonephritis following challenge with uropathogenic E coli (UPEC) and we observed an increased number of ILC3s in the bladder during UTI. We wish to examine the role of IL22 in UTI. There are no published data of UTI models in IL22-/- mice. However, human bladder epithelial cells express IL23 and the IL22R in vitro and produce anti-microbial peptides in response to IL22. In addition, transcriptomic analysis of human kidney cells infected with UPEC show significant upregulation of CCL20, the chemokine ligand for CCR6, a receptor expressed by one subset of ILC3s8.