Pattern recognition receptors and the inflammasome in kidney disease

Leemans, Jaklien C.; Kors, Lotte; Anders, Hans‐Joachim; Florquin, Sandrine

doi:10.1038/nrneph.2014.91

Cited by 158 publications

(134 citation statements)

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“…The regulation of TLR2 and TLR4 has been implicated in the pathogenesis of various kidney diseases, including urinary tract infection, AKI, kidney transplantation, and glomerulonephritis 8 . Emerging evidence has demonstrated the pivotal roles of TLR2 and TLR4 in the perpetuation of inflammation in diabetic nephropathy 132 .…”

Section: [H2] Involvement Of Tlrsmentioning

confidence: 99%

“…DAMPs are derived from damaged or dying cells, and include small molecules (ATP and DNA), particles (uric acid crystals and exogenous noxious factors such as asbestos) and environmental insults such as UV irradiation 7 . Systemic and local low-grade inflammation and release of proinflammatory cytokines are implicated in the pathogenesis of T1DM and T2DM.Furthermore, among the vascular complications of diabetes mellitus, subclinical inflammation is also known to contribute to the pathogenesis of diabetic nephropathy 4,8,9 . In this Review we provide an update on the functional roles of Toll-like receptors (TLRs) and NOD-like receptors (NLRs) in the pathogenesis of T1DM and T2DM, and its vascular complications, namely diabetic nephropathy 10 .…”

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confidence: 99%

“…Furthermore, among the vascular complications of diabetes mellitus, subclinical inflammation is also known to contribute to the pathogenesis of diabetic nephropathy 4,8,9 . In this Review we provide an update on the functional roles of Toll-like receptors (TLRs) and NOD-like receptors (NLRs) in the pathogenesis of T1DM and T2DM, and its vascular complications, namely diabetic nephropathy 10 .…”

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confidence: 99%

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Innate immunity in diabetes and diabetic nephropathy

2015

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Abstract:The innate immune system consists of several classes of pattern recognition receptors (PRRs), including membrane-bound Toll-like receptors (TLRs) and nucleotide-binding domain leucine-rich oligomerization domain (NOD)-like receptors (NLRs).These receptors detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) in the extracellular and intracellular space. Intracellular NLRs constitute inflammasomes, which activate and release caspase-1, IL1β, and IL18 and thus initiate an inflammatory response. Systemic and local low-grade inflammation and release of proinflammatory cytokines are implicated in the development and progression of diabetes mellitus and diabetic nephropathy. TLR2, TLR4, and the NLRP3 inflammasome are critically involved in the inflammatory responses in pancreatic islets, adipose, liver and kidney tissues. This Review discusses how innate immune system-driven inflammatory processes can lead to apoptosis, tissue fibrosis, and organ dysfunction to cause insulin resistance, impaired insulin secretion, and renal failure. We propose that careful targeting of TLR2, TLR4, and NLRP3 signalling pathways may be beneficial for the treatment of diabetes mellitus and diabetic nephropathy. 2 Key points The innate immune system consists of several classes of pattern recognition receptors, including TLRs and NLRs, which detect pathogen-associated and danger-associated molecular patterns and initiate an inflammatory response  TLR2 and TLR4 are the predominant toll-like receptors expressed on pancreatic β cells that trigger an inflammatory response in insulitis during type 1 diabetes mellitus  TLR2 and TLR4 signaling, and activation of NLRP3 inflammasomes results in production of various proinflammatory cytokines that can induce insulin resistance in type 2 diabetes mellitus (T2DM) and obesity  Innate immune responses in T2DM and obesity are modulated by the status of the gut microbiota, autophagy, and adipokines  TLR2, TLR4, NOD2, and NLRP3 inflammasome-mediated inflammation are involved in the perpetuation of inflammation in diabetic nephropathy  The activation of TLRs and NLRs stimulates the expression of MCP-1, which is associated with the progression of diabetic nephropathy [H1] IntroductionThe prevalence of diabetes mellitus is estimated to be 8.3%, affecting ~387 million people as of 2014. The number of patients living with diabetes mellitus is expected to increase to ~592 million by 2035, as reported by the International Diabetes Federation 1 . The incidence of end-stage renal disease (ESRD) is also rapidly increasing worldwide but varies up to 15-fold by country. In 2012, the number of new diagnoses of ESRD worldwide ranged from 25 to 467 patients per million. The proportion of new cases of ESRD with diabetes mellitus as the primary cause also differs by country, with 66% cases reported in Singapore and 12-16% cases reported in Ukraine, Romania, and the Netherlands 2 . Although intensified multifactorial intervention in patients with type 2 diabete...

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Section: [H2] Involvement Of Tlrsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Innate immunity in diabetes and diabetic nephropathy

2015

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“…It is independent of the cause of kidney injury and can be detected in acute kidney failure and chronic kidney allograft nephropathy, autoimmune diseases like lupus nephritis or granulomatosis with polyangiitis, and even diabetic nephropathy. Chronic inflammation does not seem to be triggered by pathogens be it viruses, bacteria, or bacterial products (Leemans et al 2014).…”

mentioning

confidence: 99%

“…During the last few years, numerous endogenous ligands have been identified that can bind to damage-associated molecular patterns (DAMPs) and trigger inflammation by activating nuclear factor kappa b and secreting cytokines and chemokines (Leemans et al 2014). The resulting kidney tissue damage is associated with the release of more endogenous ligands and, therefore, ends in a self-sustaining vicious circle.…”

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confidence: 99%

Blocking innate immunity to slow the progression of chronic kidney disease

Schmaderer

Heemann

2014

Naunyn-Schmiedeberg's Arch Pharmacol

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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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Pattern recognition receptors and the inflammasome in kidney disease

Cited by 158 publications

References 186 publications

Innate immunity in diabetes and diabetic nephropathy

Innate immunity in diabetes and diabetic nephropathy

Blocking innate immunity to slow the progression of chronic kidney disease

Sensing context: Inhibitory receptors on non‐hematopoietic cells

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