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- Title
NFkB1 inhibits memory formation and supports effector function of ILC2s in memorydriven asthma.
- Authors
Verma, Mukesh; Verma, Divya; Sripada, Anand Santosh; Sirohi, Kapil; Varma, Rangati; Sahu, Anita; Alam, Rafeul
- Abstract
Background: ILC2s are capable of generating memory. The mechanism of memory induction and memory-driven effector function (trained immunity) in ILC2s is unknown. Objective: NFkB1 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, realtime PCR, western blot, flow cytometry and immunofluorescence staining. Results: NFkB1 was essential for the effector phase of memory-driven asthma. NFkB1 was critical for IL33 production, ILC2 generation, and production of type2 cytokines, which resulted in eosinophilic inflammation and other features of asthma. NFkB1 induction of type-2 cytokines in ILC2s was independent of GATA3. NFkB1 was important for allergen induction of ILC3s and FoxP3+ Tregs. NFkB1 did not affect Th2 cells or their cytokine production. In contrast to its protagonistic role in the effector phase, NFkB1 had an antagonistic role in the memory phase. NFkB1 inhibited allergen-induced upregulation of memoryassociated repressor and preparedness genes in ILC2s. NFkB1 upregulated RUNX1. NFkB1 formed a heterodimer with RUNX1 in ILC2s. Conclusions: NFkB1 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 NFkB1-RUNX1 heterodimer represented a non-canonical transcriptional activator of type-2 cytokines in ILC2
- Subjects
NF-kappa B; IMMUNE response; TH2 cells; INTRANASAL administration; ASTHMA
- Publication
Frontiers in Immunology, 2023, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2023.1217776