NOD‐Like Receptors

Abstract

NOD‐like receptors (NLRs) are a family of pattern recognition receptors (PRRs), able to respond to conserved microbial structures and endogenous danger signals. NLRs modulate the inflammatory response via multiple pathways including NFκB (nuclear factor kappa‐light chain‐enhancer of activated B cells)‐activation, MAPKs, ERK and inflammasome formation, which results in IL‐1β release. They act in synergy with other PRRs, bridging innate to adaptive immunity. Moreover, some NLRs directly modulate adaptive immunity via transcriptional regulation of MHC (major histocompatibility complex) class I and class II. Their essential role in orchestrating inflammatory responses is seen via their association with morbidity. NLR dysfunction can result in cancer and autoinflammatory diseases, such as Crohn's disease and ulcerative colitis, pointing out their important role in maintaining gut homeostasis. Key Concepts NLRs are an intracellular subclass of PRRs that recognise microbe‐associated molecular patterns (MAMPs) and danger‐associated molecular patterns (DAMPs). NLRs are found in different animal species and have homologues in plants. NLRs share a common tripartite structure, typically consisting of an N ‐terminal domain from the death‐fold family, a central NACHT domain and a variable number of C ‐terminal LRRs. Activation of NLRs primes innate and adaptive immunity and drives the expression of MHC class I and class II genes. Some NLRs form inflammasomes, multiprotein platforms for caspase‐1 activation and IL‐1β release. NLRs maintain gut homeostasis, differentiating between commensals and pathogens. Mutations in NLRs can lead to severe autoinflammatory diseases, cancer, dysregulation of gut homeostasis and innate immune responses. Evidence suggests that some NLRs are further implicated in development. The function of some of the 22 human NLR proteins remains elusive.

NLRP10 Affects the Stability of Abin-1 To Control Inflammatory Responses

“…NLRP1, NLRP3, and NLRC4 are among the best-characterized NLRs that activate inflammasome assembly by their oligomerization and recruitment of the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) via their PYD, resulting in the activation of procaspase-1. Caspase-1 subsequently processes the proinflammatory cytokines pro-ILb and pro-IL-18, which are involved in a range of cellular processes (2,3). In contrast to the inflammasome-forming NLRs, the NF-kB/MAPK-signaling NLRs, exemplified by NOD1 and NOD2, contain a CARD N-terminal domain.…”

Angeborene Immunität und Adipositas – Die Rolle der Nod-like-Rezeptoren (NLR)

“…le caspase-activating and recruitment domain (CARD), verbunden mit einer acidic transactivation domain (AD), NLRBs enthalten eine baculovirus inhibitor of apoptosis protein repeat (BIR) Domäne [15,16,18]. Für Vertreter dieser beiden NLR-Subklassen sind bisher keine Zusammenhänge mit Adipositas beschrieben, weshalb sie in diesem Übersichtsartikel nicht weiter diskutiert werden.…”

“…NLRCs tragen am C-Terminus eine CARD-Domäne, zugehörig sind die Proteine NOD1 (NLRC1), NOD2 (NLRC2), NLRC3, NLRC4 und NLRC5. Die Effektordomäne der NLRPs besteht aus einer Pyrin-Domäne (PYD), die entsprechenden NLRs werden als NLRP1 -14 bezeichnet [15,16,18]. Die Strukturen der in diesem Artikel behandelten NLRs sind in ▶ Abb.…”

“…NLRs haben vielfältige Funktionen, am besten verstanden ist ihre Rolle in der Induktion von Entzündungsreaktionen [15]. So induzieren NOD1/2 beispielsweise über das Adaptermolekül RIP2 (Receptor-interacting serine/threonine-protein kinase 2) proinflammatorische Antworten durch die Aktivierung des nuclear factor ,kappa-light-chain-enhancer' of activated B-cells (NF-κB) [16] (▶ Abb. 2).…”

“…Aber nicht nur in Entzündungsprozessen spielen NLRs eine wichtige Rolle. NLRC5 und CIITA (Class II Major Histocompatibility Complex Transactivator) sind essenziell für die Transkription von MHC-Klasse-I-und MHC-Klasse-II-Genen und fungieren somit als transkriptionelle Aktivatoren und Verbindungsmoleküle zwischen der angeborenen und der adaptiven Immunantwort [16,23,24].…”