Cell type-specific roles of NLRP3, inflammasome-dependent and -independent, in host defense, sterile necroinflammation, tissue repair, and fibrosis

Honda, Tamisa Seeko Bandeira; Ku, John; Anders, Hans‐Joachim

doi:10.3389/fimmu.2023.1214289

Cited by 8 publications

(2 citation statements)

References 136 publications

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“…In general, inflammasomes are considered restricted to myeloid cells, including monocytes, macrophages, dendritic cells and neutrophils. However, the presence of the NLRP3 inflammasome components has also been reported in epithelial and parenchymal cells 7 …”

Section: Immune Cell Functions and Their Distinguishing Featuresmentioning

confidence: 99%

Not an immune cell, but they may act like one—cells with immune properties outside the immune system

Typiak,

Żurawa‐Janicka

2024

Immunol Cell Biol

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The cells presented in this work are not classified as cells that make up the immune system. They, however, present functions and molecules, which are characteristic of immune cells. These characteristic functions are, for example, sensing threat, performing phagocytosis, presentation of foreign antigens, cytokine release or enhancing immune memory. The enlisted immune response mechanisms are carried out by the possession of molecules such as Toll‐like receptors, receptors for the Fc fragment of IgG, major histocompatibility complex class II molecules, costimulatory CD80/CD86 proteins and molecules needed for NLRP3 (NOD‐like family pyrin domain containing 3) inflammasome activation. Thanks to these properties, the described nonimmune cells play an important role in the local immune response and support of the entire body in the fight against pathogens. They constitute the first line of defense of tissues and organs against pathogens and molecules recognized as harmful. The cells described in this article are particularly important in immunologically privileged places (e.g. the Bowman's capsule in the kidney), where “typical” immune cells normally do not have access. In this paper, we present immune‐like functions and molecule suites of resident kidney cells (podocytes and mesangial cells), cochlear resident cells, fibrocytes and fibroblasts, as well as some stem cells (mesenchymal stem cells and umbilical cord Wharton's jelly–derived cells).

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Section: Immune Cell Functions and Their Distinguishing Featuresmentioning

confidence: 99%

Not an immune cell, but they may act like one—cells with immune properties outside the immune system

Typiak,

Żurawa‐Janicka

2024

Immunol Cell Biol

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“…The Nlrp3 inflammasome has been recognized to be the most vital target for delaying/treating several disorders, as its activation is evoked through a wide range of stress inducers, such as pathogens, toxins, degenerative/dead cells and damaged DNA/RNA aggregates, which are called pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) [17,22]. It has also been shown that multiple pathways and mechanisms can be involved in the activation of the Nlrp3 inflammasome depending upon cell/tissue types [37][38][39][40]. ROS have been identified to be one of the critical elements for Nlrp3 inflammasome activation [38,41].…”

Section: Introductionmentioning

confidence: 99%

Prdx6 Regulates Nlrp3 Inflammasome Activation-Driven Inflammatory Response in Lens Epithelial Cells

Chhunchha,

Kumar,

Kubo

et al. 2023

IJMS

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The continuum of antioxidant response dysregulation in aging/oxidative stress-driven Nlrp3 inflammasome activation-mediated inflammatory response is associated with age-related diseases. Peroxiredoxin (Prdx) 6 is a key antioxidant that provides cytoprotection by regulating redox homeostasis. Herein, using lens epithelial cells (LECs) derived from the targeted inactivation of Prdx6 gene and aging lenses, we present molecular evidence that Prdx6-deficiency causes oxidative-driven Nlrp3 inflammasome activation, resulting in pyroptosis in aging/redox active cells wherein Prdx6 availability offsets the inflammatory process. We observed that Prdx6−/− and aging LECs harboring accumulated reactive oxygen species (ROS) showed augmented activation of Nlrp3 and bioactive inflammatory components, like Caspase-1, IL-1β, ASC and Gasdermin-D. Similar to lipopolysaccharide treatment, oxidative exposure led to further ROS amplification with increased activation of the Nlrp3 inflammasome pathway. Mechanistically, we found that oxidative stress enhanced Kruppel-like factor 9 (Klf9) expression in aging/Prdx6−/− mLECs, leading to a Klf9-dependent increase in Nlrp3 transcription, while the elimination of ROS by the delivery of Prdx6 or by silencing Klf9 prevented the inflammatory response. Altogether, our data identify the biological significance of Prdx6 as an intrinsic checkpoint for regulating the cellular health of aging or redox active LECs and provide opportunities to develop antioxidant-based therapeutic(s) to prevent oxidative/aging-related diseases linked to aberrant Nlrp3 inflammasome activation.

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Biological and therapeutic significance of targeting NLRP3 inflammasome in the brain and the current efforts to develop brain-penetrant inhibitors

Kaur,

Biby,

Namme

et al. 2024

Advances in Pharmacology

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Cell type-specific roles of NLRP3, inflammasome-dependent and -independent, in host defense, sterile necroinflammation, tissue repair, and fibrosis

Cited by 8 publications

References 136 publications

Not an immune cell, but they may act like one—cells with immune properties outside the immune system

Not an immune cell, but they may act like one—cells with immune properties outside the immune system

Prdx6 Regulates Nlrp3 Inflammasome Activation-Driven Inflammatory Response in Lens Epithelial Cells

Biological and therapeutic significance of targeting NLRP3 inflammasome in the brain and the current efforts to develop brain-penetrant inhibitors

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