Potentiation and tolerance of toll-like receptor priming in human endothelial cells

Koch, Stephen R.; Lamb, Fred S.; Hellman, Judith; Sherwood, Edward R.; Stark, Ryan J.

doi:10.1016/j.trsl.2016.08.001

Cited by 24 publications

(19 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The chromatin landscape in stromal memory is receiving increasing attention. When EC were primed with TLR‐3 agonist, the CXCL10 induction by subsequent TLR‐4 agonist was augmented and this was reduced by inhibiting histone deacetylases . This suggests that the induction of chromatin opening is part of the augmented stromal memory response.…”

Section: Mechanisms Underpinning Innate Memorymentioning

confidence: 99%

“…As seen in fibroblast memory, some authors have not found an altered response to second challenge , while others have shown both positive and negative memory responses indicative of a complex interplay of stimuli and cellular pathways. The examination of cross‐stimulation (initial and secondary stimuli inducing different pathways) has led to the conclusion that some mechanisms of innate memory are shared with the myeloid lineage , but not all observations match, suggesting cell‐ and stimulus‐specific pathways.…”

Section: Stroma In Inflammationmentioning

confidence: 99%

See 1 more Smart Citation

Stroma: the forgotten cells of innate immune memory

Crowley

Buckley

Clark

2018

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryAll organisms are exposed constantly to a variety of infectious and injurious stimuli. These induce inflammatory responses tailored to the threat posed. While the innate immune system is the front line of response to each stimulant, it has been considered traditionally to lack memory, acting in a generic fashion until the adaptive immune arm can take over. This outmoded simplification of the roles of innate and acquired arms of the immune system has been challenged by evidence of myeloid cells altering their response to subsequent encounters based on earlier exposure. This concept of ‘innate immune memory’ has been known for nearly a century, and is accepted among myeloid biologists. In recent years other innate immune cells, such as natural killer cells, have been shown to display memory, suggesting that innate immune memory is a trait common to several cell types. During the last 30 years, evidence has slowly accumulated in favour of not only haematopoietic cells, but also stromal cells, being imbued with memory following inflammatory episodes. A recent publication showing this also to be true in epithelial cells suggests innate immune memory to be widespread, if under‐appreciated, in non‐haematopoietic cells. In this review, we will examine the evidence supporting the existence of innate immune memory in stromal cells. We will also discuss the ramifications of memory in long‐lived tissue‐resident cells. Finally, we will pose questions we feel to be important in the understanding of these forgotten cells in the field of innate memory.

show abstract

Section: Mechanisms Underpinning Innate Memorymentioning

confidence: 99%

Section: Stroma In Inflammationmentioning

confidence: 99%

Stroma: the forgotten cells of innate immune memory

Crowley

Buckley

Clark

2018

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…More recently, other TLRs have been investigated as potentially involved in APS pathogenesis. TLR3 activation via polyinosinic:polycytidylic acid (Poly I:C) seems to enhance LPS/TLR4-induced production of Interferon (IFN) [80]. TLR9 recognizes viral and bacterial DNA, which contain unmethylated CpG dinucleotides.…”

Section: Endothelial Perturbation In Anti-phospholipid Antibody Syndromementioning

confidence: 99%

Vitamin D and Anti-Phospholipid Antibody Syndrome: A Comprehensive Review

Gualtierotti¹,

Giacomo²,

Raschi³

et al. 2018

Open Rheumatol. J.

View full text Add to dashboard Cite

Vitamin D is a steroid hormone that exerts a variety of biological effects that range from the well-known regulation of bone metabolism to the modulation of cellular growth, of apoptosis, and the regulation of both innate and adaptive immunity. Evidence supports a correlation between low vitamin D levels and a high risk to develop chronic inflammatory diseases including autoimmune diseases. Anti-phospholipid antibody (aPL) syndrome (APS) is an autoimmune chronic condition characterized by recurrent arterial and/or venous thrombosis and/or obstetric complications associated with persistent aPL positivity. Secondary prevention of thrombosis is widely accepted in these patients and relies on lifelong anticoagulant drugs. On the contrary, primary prevention in isolated aPL positivity in healthy carriers and treatment of obstetric manifestations in APS are still debated. Epidemiological data have shown that vitamin D deficiency (serum levels <30 ng/ml) is frequent in APS patients and that it may be associated with an increased risk of thrombosis in these patients. Experimental data show that vitamin D is able to reduce the expression of adhesion molecules, of toll-like receptors and the secretion of proinflammatory chemokines, thus playing a protective role on endothelial activation and the subsequent development of thrombosis in APS. Although these observations need to be confirmed in prospective studies and randomized clinical trials, it is tempting to speculate that vitamin D supplementation could be very useful for the prevention of clinical manifestations in APS patients, in particular as a primary prevention countermeasure in aPL carriers.

show abstract

“…The phenotype of endotoxin tolerance and cross-tolerance has been extensively studied in monocytes and macrophages, even though the majority of innate immune cells develop tolerance to secondary TLR stimuli. These include dendritic cells, neutrophils, mast cells as well as endothelial and epithelial cells ( 10 – 14 ).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Endotoxin Tolerance and Compensatory Anti-inflammatory Response Syndrome by Non-coding RNAs

2018

View full text Add to dashboard Cite

The onset and the termination of innate immune response must be tightly regulated to maintain homeostasis and prevent excessive inflammation, which can be detrimental to the organism, particularly in the context of sepsis. Endotoxin tolerance and compensatory anti-inflammatory response syndrome (CARS) describe a state of hypo-responsiveness characterized by reduced capacity of myeloid cells to respond to inflammatory stimuli, particularly those initiated by bacterial lipopolysaccharide (LPS). To achieve endotoxin tolerance, extensive reprogramming otherwise termed as “innate immune training”, is required that leads to both modifications of the intracellular components of TLR signaling and also to alterations in extracellular soluble mediators. Non-coding RNAs (ncRNAs) have been recognized as critical regulators of TLR signaling. Specifically, several microRNAs (miR-146, miR-125b, miR-98, miR-579, miR-132, let-7e and others) are induced upon TLR activation and reciprocally promote endotoxin tolerance and/or cross tolerance. Many other miRNAs have been also shown to negatively regulate TLR signaling. The long non-coding (lnc)RNAs (Mirt2, THRIL, MALAT1, lincRNA-21 and others) are also altered upon TLR activation and negatively regulate TLR signaling. Furthermore, the promotion or termination of myeloid cell tolerance is not only regulated by intracellular mediators but is also affected by other TLR-independent soluble signals that often achieve their effect via modulation of intracellular ncRNAs. In this article, we review recent evidence on the role of different ncRNAs in the context of innate immune cell tolerance and trained immunity, and evaluate their impact on immune system homeostasis.

show abstract

Potentiation and tolerance of toll-like receptor priming in human endothelial cells

Cited by 24 publications

References 53 publications

Stroma: the forgotten cells of innate immune memory

Stroma: the forgotten cells of innate immune memory

Vitamin D and Anti-Phospholipid Antibody Syndrome: A Comprehensive Review

Regulation of Endotoxin Tolerance and Compensatory Anti-inflammatory Response Syndrome by Non-coding RNAs

Contact Info

Product

Resources

About