NLRC3

Last update 08 May 2025

Basic Info

Synonyms

CARD15-like protein, Caterpiller protein 16.2, CLR16.2

+ [9]

Introduction

Negative regulator of the innate immune response (PubMed:15705585, PubMed:22863753, PubMed:25277106). Attenuates signaling pathways activated by Toll-like receptors (TLRs) and the DNA sensor STING/TMEM173 in response to pathogen-associated molecular patterns, such as intracellular poly(dA:dT), but not poly(I:C), or in response to DNA virus infection, including that of Herpes simplex virus 1 (HSV1) (By similarity) (PubMed:22863753). May affect TLR4 signaling by acting at the level of TRAF6 ubiquitination, decreasing the activating 'Lys-63'-linked ubiquitination and leaving unchanged the degradative 'Lys-48'-linked ubiquitination (PubMed:22863753). Inhibits the PI3K-AKT-mTOR pathway possibly by directly interacting with the posphatidylinositol 3-kinase regulatory subunit p85 (PIK3R1/PIK3R2) and disrupting the association between PIK3R1/PIK3R2 and the catalytic subunit p110 (PIK3CA/PIK3CB/PIK3CD) and reducing PIK3R1/PIK3R2 activation. Via its regulation of the PI3K-AKT-mTOR pathway, controls cell proliferation, predominantly in intestinal epithelial cells (By similarity). May also affect NOD1- or NOD2-mediated NF-kappa-B activation (PubMed:25277106). Might also affect the inflammatory response by preventing NLRP3 inflammasome formation, CASP1 cleavage and IL1B maturation (PubMed:25277106).

100 Clinical Results associated with NLRC3

100 Translational Medicine associated with NLRC3

0 Patents (Medical) associated with NLRC3

357

Literatures (Medical) associated with NLRC3

01 Dec 2025·Inflammation Research

The role of NLRP3 inflammasome-mediated pyroptosis in astrocytes during hyperoxia-induced brain injury

Review

Author: Liu, Qiao ; Han, Lei ; Tang, Wang ; Tian, Gui-Xiang ; Tan, Yan ; Liu, Ming-Hui ; Zhang, Zhan-Wei ; Peng, Ke-Ping

BACKGROUNDHyperoxia-induced brain injury is a severe neurological complication that is often accompanied by adverse long-term prognosis. The pathogenesis of hyperoxia-induced brain injury is highly complex, with neuroinflammation playing a crucial role. The activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, which plays a pivotal role in regulating and amplifying the inflammatory response, is the pathological core of hyperoxia-induced brain injury. Additionally, astrocytes actively participate in neuroinflammatory responses. However, there is currently no comprehensive overview summarizing the role of astrocytes in hyperoxia-induced brain injury and the NLRP3 signaling pathways in astrocytes.OBJECTIVEThis article aims to provide an overview of studies reported in the literature investigating the pathological role of astrocyte involvement during the inflammatory response in hyperoxia-induced brain injury, the mechanisms of hyperoxia activateing the NLRP3 inflammasome to mediate pyroptosis in astrocytes, and the potential therapeutic effects of drugs targeting the NLRP3 inflammasome to alleviate hyperoxia-induced brain injury.METHODWe searched major databases (including PubMed, Web of Science, and Google Scholar, etc.) for literature encompassing astrocytes, NLRP3 inflammasome, and pyroptosis during hyperoxia-induced brain injury up to Oct 2024. We combined with studies found in the reference lists of the included studies.CONCLUSIONIn this study, we elucidated the transition of function in astrocytes and activation mechanisms under hyperoxic conditions, and we summarized the potential upstream of the trigger involved in NLRP3 inflammasome activation during hyperoxia-induced brain injury, such as ROS and potassium efflux. Furthermore, we described the signaling pathways of the NLRP3 inflammasome and pyroptosis executed by GSDMD and GSDME in astrocytes under hyperoxic conditions. Finally, we summarized the inhibitors targeting the NLRP3 inflammasome in astrocytes to provide new insights for treating hyperoxia-induced brain injury.

01 Jul 2025·Fish & Shellfish Immunology

NLRC3 regulates RIP2, STING, TBK1, and TRAF6 mediated type I IFN signaling and inflammatory response in large yellow croaker Larimichthys crocea

Article

Author: Li, Kai Qing ; Zou, Peng Fei ; Li, Ying ; Sun, Zhao Han ; Zhang, Jia Xi ; Jiang, Yong Hua ; Xu, Yu Qing ; Jiang, Jing ; Han, Kun Huang ; Wang, Yi Lei

As a member of the NLRs family, NLRC3 has been determined to function in the NF-κB, MAPK, and type I IFN signaling, which are crucial for the host innate immunity and inflammatory response. In this study, an NLRC3 ortholog, named as Lc-NLRC3, was cloned and identified in large yellow croaker (Larimichthys crocea). The gene characteristics analysis revealed that Lc-NLRC3 consists of 18 exons and 17 introns, with a full-length open reading frame (ORF) of 3405 bp, encoding a protein of 1134 amino acids (aa), that containing a N-terminal CARD domain, a central NACHT domain, and a C-terminal LRRs domain. It was shown that Lc-NLRC3 is predominantly found in the cytosol, and was widely distributed across various tissues/organs, with the highest expression detected in the intestine, and could be induced by poly I:C, LPS, PGN, and Pseudomonas plecoglossicida stimulation. Importantly, Lc-NLRC3 overexpression significantly activate NF-κB, TNFα, IL-1β, IRF3, IRF7, and IFN1 promoters, whereas when co-expressed with RIP2, STING, or TBK1, it down-regulated those promoter activation compared to their individual overexpression alone, thereby suppressing downstream antiviral and inflammatory gene expression. Interestingly, Lc-NLRC3 associated with TRAF6 in IRF3/IRF7 promoter activation, and enhanced the expression of IRF7, Mx, ISG15, and TNF-α. Co-immunoprecipitation assays also confirmed interactions of Lc-NLRC3 with RIP2, STING, TBK1, and TRAF6. The above results imply that Lc-NLRC3 is an important regulator in RIP2, STING, TBK1, and TRAF6 mediated type I IFN signaling and inflammatory response.

01 Jun 2025·Theriogenology

Dual roles of the TLR2/TLR4/NLRP3-H-PGDS-PGD2 axis in regulating the inflammatory response in Escherichia coli-infected bovine bone marrow-derived macrophages and endometrial tissue

Article

Author: Wang, Yongfei ; Yang, Xiaolin ; Mao, Wei ; Wu, Jingze ; Zhang, Shuangyi ; Guo, Lili ; Cao, Jinshan ; Liu, Bo ; Gong, Pengfei ; Zhao, Yi ; Hasi, Surong

Endometritis in dairy cows is associated with pathogenic microorganisms, local inflammatory injuries, and uterine microecological disorders. Escherichia coli (E. coli) is the primary pathogen responsible for bovine endometritis onset; however, the underlying pathomechanisms remain unclear. In this study, we aimed to investigate E. coli-induced endometritis mechanisms in dairy cows using bovine bone marrow-derived macrophages and endometrial tissue. Following E. coli infection of macrophages, we observed a significant increase in the mRNA expression levels of innate immune recognition receptors, including toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), as well as prostaglandin D₂ (PGD₂)-related enzymes (cyclooxygenase-2 and hematopoietic prostaglandin D synthase). Furthermore, the secretion of PGD₂, a major mediator of inflammation, was markedly upregulated. In E. coli-infected macrophages, TLR2, TLR4, and NLRP3 increased the secretion of inflammatory mediators, including PGD₂, by activating mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB). This lead to enhanced inflammatory response. During early E. coli infection, PGD₂ inhibitors reduced the secretion of inflammatory mediators by modulating MAPK and NF-κB pathway activation and enhancing macrophage bacterial killing, thereby alleviating endometrial tissue damage in dairy cows. In contrast, in the later stages of infection, PGD₂ inhibitors exacerbated the inflammatory response and impaired the killing capacity of macrophages, which lead to increased endometrial tissue damage. Therefore, our findings highlight that TLR2, TLR4, and NLRP3 are pivotal in regulating PGD₂ secretion during E. coli-induced endometritis in dairy cows. PGD₂ had a pro-inflammatory effect in the early stages of E. coli infection and anti-inflammatory effects in the later stages. These findings can help develop strategies benefiting endometritis treatment.

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NLRC3

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