Visualization of IL-22 expressing cells during anti-infectious immune responses

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Interleukin-22 (IL-22) is a cytokine of the IL-10 family initially found to be produced by differentiated Th17 lymphocytes. Recently, a novel population of IL-22 producing natural killer (NK)-like cells in the gut have been identified which co-express markers of the lymphoid tissue inducer (LTi) cells like RORγt and NK cells like NKp46 but have only low cytolytic or IFNγ production activity. Functionally IL-22 has been implicated in tissue repair and host defense against infections by inducing the production of defensins and regenerating gene family proteins in epithelial cells. IL-22 deficient mice, for instance, show an increased susceptibility for infections with Citrobacter rodentium and Klebsiella pneumoniae due to reduced production of anti-microbial peptides. While the general ability to produce IL-22 was demonstrated for Th17 and RORγt+ NKp46+ cells, the actual cellular source of IL-22 production during the course of an infection in different host organs is still poorly defined in vivo. The aim of the study proposed here is to generate an IL-22 reporter mouse line by inserting an IRES driven YFP fluorescence cassette behind the stop codon of the endogenous IL-22 gene locus by homologous recombination in mouse embryonic stem cells. This mouse line will be used to visualize the IL-22 producing cells in the murine lung infection models of Klebsiella pneumoniae, Chlamydia pneumoniae and Toxoplasma gondii. Findings from these experiments can later be expanded and compared to the intestinal and systemic infection models using Citrobacter rodentium and Listeria monocytogenes, respectively. As IL-22 production is dependent on IL-23 crossing the IL-22-YFP reporter to the already existing IL-12/23p40-GFP reporter mouse line will allow to simultaneously monitor the regulating IL-23 producing cells vs. the effector IL-22 producing ones. In summary the proposed project can contribute significantly to the definition of the IL-22 producing cell populations, their interaction partners, and their effector mechanisms during anti-infectious immune responses.