Inhibitory pattern recognition receptors

Rumpret, Matevž; Richthofen, Helen J. von; Peperzak, Victor; Meyaard, Linde

doi:10.1084/jem.20211463

Cited by 18 publications

(14 citation statements)

References 110 publications

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“…Recent reviews have demonstrated the multiple roles of DAMPs, which are produced or released by damaged and dying cells, in sterile inflammation and tissue repair after they are sensed by various pattern recognition receptors [ 8 , 9 ]. Currently, an increasing number of endogenous host-derived molecules, including S100 proteins, heat shock proteins, high mobility group box 1 protein (HMGB1), circulating histones and glycans such as heparan sulfate, are considered DAMPs [ 10 ]. Among them, HMGB1 and histones are abundantly studied because they significantly mediate lethal systemic inflammation, complement and coagulation activation, endothelial injury and organ dysfunction in various critical illnesses, such as sepsis [ 11 , 12 ], acute liver failure [ 13 ], pancreatitis [ 14 , 15 ], multiple trauma [ 16 ] and severe COVID-19 [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses

Chen

Yang

et al. 2023

Crit Care

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Both high mobility group box-1 (HMGB1) and histones are major damage-associated molecular patterns (DAPMs) that mediate lethal systemic inflammation, activation of the complement and coagulation system, endothelial injury and multiple organ dysfunction syndrome in critical illnesses. Although accumulating evidence collectively shows that targeting HMGB1 or histones by their specific antibodies or inhibitors could significantly mitigate aberrant immune responses in multiple critically ill animal models, routine clinical use of such agents is still not recommended by any guideline. In contrast, extracorporeal blood purification, which has been widely used to replace dysfunctional organs and remove exogenous or endogenous toxins in intensive care units, may also exert an immunomodulatory effect by eliminating inflammatory mediators such as cytokines, endotoxin, HMGB1 and histones in patients with critical illnesses. In this review, we summarize the multiple immunopathological roles of HMGB1 and histones in mediating inflammation, immune thrombosis and organ dysfunction and discuss the rationale for the removal of these DAMPs using various hemofilters. The latest preclinical and clinical evidence for the use of extracorporeal blood purification to improve the clinical outcome of critically ill patients by targeting circulating HMGB1 and histones is also gathered.

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Section: Introductionmentioning

confidence: 99%

Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses

Chen

Yang

et al. 2023

Crit Care

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“…To detect them, immune cells use pattern recognition receptors (PRRs), which include five known receptor groups: Toll-like receptors (TLRs), C-type lectin receptors (CLRs), nucleotide-binding oligomerisation domain-like receptors (NOD-like receptors, NLRs), retinoic acid-inducible gene-I-like receptors, (RIG-I-like receptors, RLRs), as well as cytoplasmic sensors such as cyclic Guanosine monophosphate-Adenosine monophosphate synthase (cyclic GMP-AMP synthase). NLR and RLR receptors are located in the cytoplasm, while TLR and CLR are located on the surface of the cell membrane or endosome membranes [ 17 ]. Once the matching molecule is recognised, cell activation and effector responses occur at several levels.…”

Section: Trained Immunity In Generalmentioning

confidence: 99%

Trained Immunity, BCG and SARS-CoV-2 General Outline and Possible Management in COVID-19

Zapolnik

Kmiecik²,

Mazur

et al. 2023

IJMS

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The Bacillus Calmette–Guérin (BCG) vaccine has been in use for over 100 years. It protects against severe, blood-borne forms of tuberculosis. Observations indicate that it also increases immunity against other diseases. The mechanism responsible for this is trained immunity, an increased response of non-specific immune cells in repeated contact with a pathogen, not necessarily of the same species. In the following review, we present the current state of knowledge on the molecular mechanisms responsible for this process. We also seek to identify the challenges facing science in this area and consider the application of this phenomenon in managing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.

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“…In addition, the human genome encodes many uncharacterized genes potentially encoding for ITIM-bearing receptors, which could also be expressed on epithelial cells [9]. CEACAM1, PVR, and CD300LF are pleiotropic receptors, each responding to multiple endogenous and microbial patterns ( [17,18] and reviewed in [7]). CEACAM1 binds itself, other CEA-CAMs, and microbial Ig-fold proteins.…”

Section: Epithelial Cells Express Iprrsmentioning

confidence: 99%

Sensing context: Inhibitory receptors on non‐hematopoietic cells

Richthofen

Meyaard

2023

Eur J Immunol

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Similar to immune cells, non‐hematopoietic cells recognize microbial and endogenous threats. Their response to these stimuli is dependent on the environmental context. For example, intact intestinal epithelium expresses pattern recognition receptors (PRRs) but should tolerate commensal bacteria, while damaged epithelium should respond promptly to initiate an immune response. This indicates that non‐hematopoietic cells possess mechanisms to sense environmental context and regulate their responses. Inhibitory receptors provide context sensing to immune cells. For instance, they raise the threshold for activation to prevent overzealous immune activation to harmless stimuli. Inhibitory receptors are typically studied on hematopoietic cells, but several of these receptors are expressed on non‐hematopoietic cells. Here, we review evidence for the regulation of non‐hematopoietic cells by inhibitory receptors, focusing on epithelial and endothelial cells. We explain that inhibitory receptors on these cells can sense a wide range of signals, including cell‐cell adhesion, cell‐matrix adhesion, and apoptotic cells. More importantly, they regulate various functions on these cells, including immune activation, proliferation, and migration. In conclusion, we propose that inhibitory receptors provide context to non‐hematopoietic cells by fine tuning their response to endogenous or microbial stimuli. These findings prompt to investigate the functions of inhibitory receptors on non‐hematopoietic cells more systematically.

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Inhibitory pattern recognition receptors

Cited by 18 publications

References 110 publications

Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses

Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses

Trained Immunity, BCG and SARS-CoV-2 General Outline and Possible Management in COVID-19

Sensing context: Inhibitory receptors on non‐hematopoietic cells

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