The transcription factor Rfx7 limits metabolism of NK cells and promotes their maintenance and immunity

Castro, Wilson; Chelbi, Sonia T.; Niogret, Charlène; Ramon-Barros, Cristina; Welten, Suzanne P. M.; Osterheld, Kevin; Wang, Haiping; Rota, Giorgia; Morgado, Leonor; Vivier, Éric; Raeber, Miro E.; Boyman, Onur; Delorenzi, Mauro; Barras, David; Ho, Ping‐Chih; Oxenius, Annette; Guarda, Greta

doi:10.1038/s41590-018-0144-9

Cited by 48 publications

(52 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NK cells also undergo functional exhaustion during chronic inflammation [131] and may contribute to clinical responses following PD-1 blockade [132,•133] [136] also appear to be highly relevant checkpoint receptors in NK cell functional exhaustion. Furthermore, a wealth of new studies indicate the metabolism stringently regulates the function of NK cells [137][138][139][140][141][142][143], which can limit their antiviral capacity in the context of CMV or HCV infection [144,•145].…”

Section: Nk Cell Exhaustionmentioning

confidence: 99%

Mutually assured destruction: the cold war between viruses and natural killer cells

Ali

Gyurova

Waggoner

2019

Current Opinion in Virology

View full text Add to dashboard Cite

Natural killer (NK) cells play a multitude of antiviral roles that are significant enough to provoke viral counterefforts to subvert their activity. As innate lymphocytes, NK cells provide a rapid source of pro-inflammatory antiviral cytokines and bring to bear cytolytic activities that are collectively meant to constrain viral replication and dissemination. Additionally, NK cells participate in adaptive immunity both by shaping virus-specific T-cell responses and by developing adaptive features themselves, including enhanced antibody-dependent effector functions. The relative importance of different functional activities of NK cells are poorly understood, thereby obfuscating clinical use of these cells. Here we focus on opposing efforts of NK cells and viruses to gain tactical superiority during infection.

show abstract

Section: Nk Cell Exhaustionmentioning

confidence: 99%

Mutually assured destruction: the cold war between viruses and natural killer cells

Ali

Gyurova

Waggoner

2019

Current Opinion in Virology

View full text Add to dashboard Cite

show abstract

“…We therefore examined the cells for signs of metabolic reprogramming. Scatter has been used as an indicator of metabolic alteration in NK cells (Castro et al, 2018) and we found that side scatter increased in NK cells from the livers of obese mice ( Figure 5a). NK cells use mTOR for nutrient sensing and it also has an important role in immune regulation (O'Brien and Finlay, 2019).…”

Section: Nk Cells In Obese Mice Are Metabolically Reprogrammedmentioning

confidence: 93%

TGFβ in the obese liver mediates conversion of NK cells to a less cytotoxic ILC1-like phenotype

Cuff

Sillito

Dertschnig

et al. 2019

Preprint

View full text Add to dashboard Cite

The liver contains both NK cells and their less cytotoxic relatives, ILC1. Here, we investigate the role of NK cells and ILC1 in the obesity-associated condition, non-alcoholic fatty liver disease (NAFLD). In the livers of mice suffering from NAFLD, NK cells are less able to degranulate, express lower levels of perforin and are less able to kill cancerous target cells than those from healthy animals. This is associated with a decreased ability to kill cancer cells in vivo. On the other hand, we find that perforin-deficient mice suffer from less severe NAFLD, suggesting that this reduction in NK cell cytotoxicity may be protective in the obese liver, albeit at the cost of increased susceptibility to cancer. The decrease in cytotoxicity is associated with a shift towards a transcriptional profile characteristic of ILC1, increased expression of the ILC1-associated proteins CD200R1 and CD49a, and an altered metabolic profile mimicking that of ILC1. We show that the conversion of NK cells to this less cytotoxic phenotype is at least partially mediated by TGFβ, which is expressed at high levels in the obese liver. Finally, we show that reduced cytotoxicity is also a feature of NK cells in the livers of human NAFLD patients.

show abstract

“…However, well-established ciliogenic RFX factors ( Rfx1-4 ) were not downregulated in NRF2-null MEFs [ 10 , 58 , 101 ]. Instead, reductions were seen for Rfx5 and Rfx7 , but it is unclear whether this is related to ciliogenesis, as these factors are better known as immunity regulators [ 10 , 101 , 102 , 103 ]. Alternatively, NRF2 may act on ciliogenic genes not through other transcription factors, but directly.…”

Section: Nrf2 Upregulation Of Primary Cilia and Hh Signalingmentioning

confidence: 99%

NRF2 and Primary Cilia: An Emerging Partnership

et al. 2020

View full text Add to dashboard Cite

When not dividing, many cell types target their centrosome to the plasma membrane, where it nucleates assembly of a primary cilium, an antenna-like signaling structure consisting of nine concentric microtubule pairs surrounded by membrane. Primary cilia play important pathophysiological roles in many tissues, their dysfunction being associated with cancer and ciliopathies, a diverse group of congenital human diseases. Several recent studies have unveiled functional connections between primary cilia and NRF2 (nuclear factor erythroid 2-related factor 2), the master transcription factor orchestrating cytoprotective responses to oxidative and other cellular stresses. These NRF2-cilia relationships are reciprocal: primary cilia, by promoting autophagy, downregulate NRF2 activity. In turn, NRF2 transcriptionally regulates genes involved in ciliogenesis and Hedgehog (Hh) signaling, a cilia-dependent pathway with major roles in embryogenesis, stem cell function and tumorigenesis. Nevertheless, while we found that NRF2 stimulates ciliogenesis and Hh signaling, a more recent study reported that NRF2 negatively affects these processes. Herein, we review the available evidence linking NRF2 to primary cilia, suggest possible explanations to reconcile seemingly contradictory data, and discuss what the emerging interplay between primary cilia and NRF2 may mean for human health and disease.

show abstract

The transcription factor Rfx7 limits metabolism of NK cells and promotes their maintenance and immunity

Cited by 48 publications

References 64 publications

Mutually assured destruction: the cold war between viruses and natural killer cells

Mutually assured destruction: the cold war between viruses and natural killer cells

TGFβ in the obese liver mediates conversion of NK cells to a less cytotoxic ILC1-like phenotype

NRF2 and Primary Cilia: An Emerging Partnership

Contact Info

Product

Resources

About