Understanding the regulation of pattern recognition receptors in inflammatory diseases – a ‘Nod’ in the right direction

Abstract

SummaryNucleotide-binding oligomerization domain (NOD) -like receptors (NLRs) are a family of 23 receptors known as pattern recognition receptors; they are expressed in many cell types and play a key role in the innate immune response. The NLRs are activated by pathogen-associated molecular patterns, which include structurally conserved molecules present on the surfaces of bacteria. The activation of these NLRs by pathogens results in the downstream activation of signalling kinases and transcription factors, culminating in the transcription of genes coding for pro-inflammatory factors. Expression of NLR is altered in many cellular, physiological and disease states. There is a lack of understanding of the mechanisms by which NLR expression is regulated, particularly in chronic inflammatory states. Genetic polymorphisms and protein interactions are included in such mechanisms. This review seeks to examine the current knowledge regarding the regulation of this family of receptors and their signalling pathways as well as how their expression changes in disease states with particular focus on NOD1 and NOD2 in inflammatory bowel diseases among others.

Human dendritic cells activated with MV130 induce Th1, Th17 and IL‐10 responses via RIPK2 and MyD88 signalling pathways

“…DCs are equipped with a large number of pattern recognition receptors (PRRs) that enable them to link innate and adaptive immune responses . Among them, NLRs and TLRs play essential roles in regulating human DC function including their capacity to polarize T cell responses . Interestingly, our inhibition experiments using anti‐IL‐10 blocking antibodies established the important role played by IL‐10 produced by MV130‐activated DCs in the control of excessive immune responses.…”

Microbial Host Interactions and Impaired Wound Healing in Mice and Humans: Defining a Role for BD14 and NOD2

“…H Williams et al b-Defensin 14 and Cutaneous Wound Healing in Mice and Humans factors present, such as cytokines or bacterial products (Feerick and McKernan, 2017). In this context, both NOD2 overexpression in human chronic wounds and Nod2 stimulation in murine wounds is associated with delayed wound closure.…”

Alterations in nucleotide-binding oligomerization domain-2 expression, pathway activation, and cytokine production in Yao syndrome

“…As stated earlier, specific NOD2 variants are considered as predisposing factors for CD, BS, and YAOS (1, 14, 26). In CD, the three main disease-associated NOD2 variants are associated with decreased NOD2 function, reflective of a loss-of-function genotype (2, 9).…”

“…Nucleotide-binding, oligomerization domain 2 (NOD2) is an intracellular bacterial sensor protein of the NOD-like receptor (NLR) family (1). NOD2 detects a component of the bacterial cell wall, muramyl dipeptide (MDP) and stimulates signal transduction cascades that activate NF-κB and mitogen-activated kinases (MAPKs), which in turn result in the secretion of pro-inflammatory cytokines.…”