Background: ILC2s are capable of generating memory. The mechanism of memory induction and memory-driven effector function (trained immunity) in ILC2s is unknown. Objective: NF kappa B1 is preferentially expressed at a high level in ILC2s. We examined the role of NF kappa B1 in memory induction and memory-driven effector function in a mouse model of asthma. Methods: Intranasal administration of Alternaria, flexivent, ELISA, histology, real-time PCR, western blot, flow cytometry and immunofluorescence staining. Results: NF kappa B1 was essential for the effector phase of memory-driven asthma. NF kappa B1 was critical for IL33 production, ILC2 generation, and production of type-2 cytokines, which resulted in eosinophilic inflammation and other features of asthma. NF kappa B1 induction of type-2 cytokines in ILC2s was independent of GATA3. NF kappa B1 was important for allergen induction of ILC3s and FoxP3+ Tregs. NF kappa B1 did not affect Th2 cells or their cytokine production. In contrast to its protagonistic role in the effector phase, NF kappa B1 had an antagonistic role in the memory phase. NF kappa B1 inhibited allergen-induced upregulation of memory-associated repressor and preparedness genes in ILC2s. NF kappa B1 upregulated RUNX1. NF kappa B1 formed a heterodimer with RUNX1 in ILC2s. Conclusions: NF kappa B1 positively regulated the effector phase but inhibited the induction phase of memory. The foregoing pointed to an interdependent antagonism between the memory induction and the memory effector processes. The NF kappa B1-RUNX1 heterodimer represented a non-canonical transcriptional activator of type-2 cytokines in ILC2s.
