| First Author | Verma M | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1217776 | PubMed ID | 37575259 |
| Mgi Jnum | J:340871 | Mgi Id | MGI:7519444 |
| Doi | 10.3389/fimmu.2023.1217776 | Citation | Verma M, et al. (2023) NFkappaB1 inhibits memory formation and supports effector function of ILC2s in memory-driven asthma. Front Immunol 14:1217776 |
| abstractText | BACKGROUND: ILC2s are capable of generating memory. The mechanism of memory induction and memory-driven effector function (trained immunity) in ILC2s is unknown. OBJECTIVE: NFkappaB1 is preferentially expressed at a high level in ILC2s. We examined the role of NFkB1 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: NFkappaB1 was essential for the effector phase of memory-driven asthma. NFkappaB1 was critical for IL33 production, ILC2 generation, and production of type-2 cytokines, which resulted in eosinophilic inflammation and other features of asthma. NFkappaB1 induction of type-2 cytokines in ILC2s was independent of GATA3. NFkappaB1 was important for allergen induction of ILC3s and FoxP3+ Tregs. NFkappaB1 did not affect Th2 cells or their cytokine production. In contrast to its protagonistic role in the effector phase, NFkappaB1 had an antagonistic role in the memory phase. NFkappaB1 inhibited allergen-induced upregulation of memory-associated repressor and preparedness genes in ILC2s. NFkappaB1 upregulated RUNX1. NFkappaB1 formed a heterodimer with RUNX1 in ILC2s. CONCLUSIONS: NFkappaB1 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 NFkappaB1-RUNX1 heterodimer represented a non-canonical transcriptional activator of type-2 cytokines in ILC2s. |
