Runx3 Mediates Resistance to Intracellular Bacterial Infection by Promoting IL12 Signaling in Group 1 ILC and NCR+ILC3

Innate lymphoid cells (ILCs) are the most recently identified family of the innate immune system and are hypothesized to modulate immune functions prior to the generation of adaptive immune responses. Subsets of ILCs reside in the mucosa and regulate immune responses to external pathogens; however, their role and the mechanism by which they protect against intracellular bacterial infection is not completely understood. In this report, using S. typhimurium and L. monocytogenes, we found that the levels of group 1 ILCs and NCR(+) ILC3s were increased upon infection and that these increases were associated with Runt-related transcription factor 3 (Runx3) expression. Runx3 (fl/fl) PLZF-cre mice were much more sensitive to infection with the intracellular bacterial pathogens S. typhimurium and L. monocytogenes partially due to abnormal Group 1 ILC and NCR(+)ILC3 function. We also found that Runx3 directly binds to the Il12Rβ2 promoter and intron 8 to accelerate the expression of Il12Rβ2 and modulates IFNγ secretion triggered by the IL12/ STAT4 axis. Therefore, we demonstrate that Runx3 influences group 1 ILC- and NCR+ILC3-mediated immune protection against intracellular bacterial infections of both the gut and liver.