Krüppel-like factor 3 (KLF3) suppresses NF-κB–driven inflammation in mice

Abstract

Bacterial products such as lipopolysaccharides (or endotoxin) cause systemic inflammation, resulting in a substantial global health burden. The onset, progression, and resolution of the inflammatory response to endotoxin are usually tightly controlled to avoid chronic inflammation. Members of the NF-κB family of transcription factors are key drivers of inflammation that activate sets of genes in response to inflammatory signals. Such responses are typically short-lived and can be suppressed by proteins that act post-translationally, such as the SOCS (suppressor of cytokine signaling) family. Less is known about direct transcriptional regulation of these responses, however. Here, using a combination of in vitro approaches and in vivo animal models, we show that endotoxin treatment induced expression of the well-characterized transcriptional repressor Krüppel-like factor 3 (KLF3), which, in turn, directly repressed the expression of the NF-κB family member RELA/p65. We also observed that KLF3-deficient mice were hypersensitive to endotoxin and exhibited elevated levels of circulating Ly6C+ monocytes and macrophage-derived inflammatory cytokines. These findings reveal that KLF3 is a fundamental suppressor that operates as a feedback inhibitor of RELA/p65 and may be important in facilitating the resolution of inflammation.

Single-cell transcriptome landscape of zebrafish liver reveals hepatocytes and immune cell interactions in understanding nonalcoholic fatty liver disease

“…This analysis predicted the expression networks of transcription factors that were upregulated in pro- or anti-inflammatory macrophages (Figure 3E). For instance, regulons driven by members of the IRF family were enriched in inflammatory macrophages, such as irf1 , which are essential in the development and activation of inflammatory macrophages ( 65 ), whereas KLF family members were enriched in non-inflammatory macrophages, such as klf3 , which play an important role in the inhibition of inflammation ( 66 ).…”

Eosinophil function in adipose tissue is regulated by Krüppel-like factor 3 (KLF3)

“…While the mechanisms underlying had remained unclear, evidence of enhanced beiging in Klf3 −/− mice now provides a possible explanation. The role of haematopoietic cells in AT function and thermogenesis is now widely appreciated, and KLF3 is both active in haematopoietic lineages [29][30][31][32][33] and highly expressed in a range of haematopoietic cell types according to the Immgen 34 and Haemopedia 35,36 databases. We thus focused on a possible role for KLF3 in BM haematopoietic cells that could give rise to cells occupying the AT SVF niche and regulate adipose function.…”

Acetylcholine‐synthesizing macrophages in subcutaneous fat are regulated by β 2 ‐adrenergic signaling

“…BMDMs were cultured based on previously performed protocols (Knights et al , 2016; Knights et al , 2020b; Zhu et al , 2020). Briefly, femora and tibiae were extracted from 6 to 10 week old mice, flushed, and subjected to red blood cell lysis.…”