Transcriptional Control of Group 1 Innate Lymphoid Cells

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Innate lymphoid cells (ILCs) form a recently discovered heterogeneous group of lymphocytes, which play an important role in lymphorganogenesis, the immune response against microorganisms and tissue homeostasis. In reference to T helper cells ILCs can be divided into three groups: i) group 1 ILCs produce IFNg and are dependent on the transcription factors T-bet, Eomes and/or RORgt, ii) group 2 ILCs produce Interleukin (IL)-5 and IL-13 and are dependent on the transcription factors GATA-3 and RORalpha, and iii) group 3 ILCs, which produce IL-17 and IL-22, depend on the transcription factor RORgt. So far two distinct lineages have been detected withihn group 1 ILCs; i) conventional NK cells that express T-bet and Eomes and ii) cells which originally develop from group 3 ILCs but loose RORgt during their differentiation (Ex-RORgt) while maintaining T-bet expression. To clarify whether there is an additional lineage of group 1 ILCs, we have established a reporter mouse strain, which enables to us to identify classical NK cells and Ex-RORgt group 1 ILCs within the same mouse. Analysis of these mice revealed that there is a third population of group 1 ILCs, primarily present in the lamina propria of the gut and the mesenteric lymph nodes. We now want to thoroughly examine this newly identified population of group 1 ILCs with respect to development, function and transcriptional control and compare it with the other group 1 ILC populations (i.e. NK cells and Ex-RORgt ILCs). The fact that ILCs exercise manifold functions makes them an interesting target for pharmaceutical intervention. The proposed study aims at identifying unique signalling pathways and functional properties within different group 1 ILCs. In the long term this will be instrumental for the design of drugs that will interfere with specific group 1 ILCs.