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Innate immune cells play important roles in tissue injury and repair following acute myocardial infarction (MI). Although reprogramming of macrophage metabolism has been observed during inflammation and resolution phases, the mechanistic link to macrophage phenotype is not fully understood. In this study, we found that myeloid-specific deletion (mKO) of mitochondrial complex I protein, encoded by Ndufs4, reproduced the proinflammatory metabolic profile in macrophages and exaggerated the response to LPS. Moreover, mKO mice showed increased mortality, poor scar formation, and worsened cardiac function 30 days after MI. We observed a greater inflammatory response in mKO mice on day 1 followed by increased cell death of infiltrating macrophages and blunted transition to the reparative phase during post-MI days 3-7. Efferocytosis was impaired in mKO macrophages, leading to lower expression of antiinflammatory cytokines and tissue repair factors, which suppressed the proliferation and activation of myofibroblasts in the infarcted area. Mitochondria-targeted ROS scavenging rescued these impairments, improved myofibroblast function in vivo, and reduced post-MI mortality in mKO mice. Together these results reveal a critical role of mitochondria in inflammation resolution and tissue repair via modulation of efferocytosis and crosstalk with fibroblasts. These findings have potential significance for post-MI recovery as well as for other inflammatory conditions., Introduction Innate immune cells, such as monocytes and macrophages, play vital roles in tissue injury and repair. Cell death caused by myocardial ischemia in the infarct region recruits and activates [...]

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 [ABSTRACT FROM AUTHOR]