NLRC5 Negatively Regulates the NF-κB and Type I Interferon Signaling Pathways

Cui, Jun; Zhu, Liang; Xia, Xiaojun; Wang, Helen Y.; Legras, Xavier; Hong, Jun; Ji, Jiabing; Shen, Pingping; Zheng, Shu; Chen, Zhijian J.; Wang, Rong Fu

doi:10.1016/j.cell.2010.03.040

Cited by 386 publications

(482 citation statements)

References 42 publications

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“…NLRC5 is also expressed abundantly in lung and intestine, which have close contact with microorganism. More specifically, NLRC5 is found highly expressed in immune cells including mouse primary cells such as bone marrow-derived macrophages (BMDMs), splenic DCs, CD4 + T cells, CD8 + T cells and B cells as well as in cell lines such as human THP-1, Jurkat T cells, Raji B cells and mouse RAW264.7 (Benko et al, 2010;Cui et al, 2010;Neerincx et al, 2010). While NLRC5 is constitutively expressed in many immune cells, it can also be dramatically induced by a variety of stimulations.…”

Section: Expression Of Nlrc5mentioning

confidence: 99%

“…Interferon-γ (IFN-γ) is a widely reported stimulus capable of strongly inducing NLRC5 expression at both mRNA and protein level in various cell types like lymphocytes (CD4 + T cells, CD8 + T cells), myeloid cells (macrophage or dendritic cells), fibroblasts and Hela cells (Benko et al, 2010;Neerincx et al, 2010;Staehli et al, 2012). LPS is also confi rmed to induce a high level of NLRC5 transcription and expression (Cui et al, 2010;Staehli et al, 2012;Yao et al, 2012). Interestingly, this up-regulation was dependent on TRIF but not MyD88, which were adaptors of TLR4 downstream signaling and mediate type I interferon (IFN) producing pathway and NF-κB activation pathway respectively, implying that type I interferon may induce NLRC5 expression.…”

Section: Expression Of Nlrc5mentioning

confidence: 99%

“…Based on these discoveries, STAT1 is suggested to play an essential role in the regulation of NLRC5 expression (Staehli et al, 2012). NLRC5 has also been observed to be induced by diversifi ed bacteria and virus, or their PAMPs like poly(I:C), CpG and poly(dA:dT) which all can induce type I IFN (Cui et al, 2010;Kuenzel et al, 2010;Staehli et al, 2012;Yao et al, 2012). Therefore, both type I and type II IFN can strongly induce NLRC5 expression through STAT1 dependent pathway.…”

Section: Structure Of Nlrc5mentioning

confidence: 99%

“…While the role of NLRC5 in regulating MHC class I gene expression is well recognized by intensive studies, previous researches suggested that NLRC5 may also regulate innate immune responses through affecting TLR mediated NF-κB activation, type I interferon (IFN)-producing pathways as well as inflammasome activation (Benko et al, 2010;Cui et al, 2010;Neerincx et al, 2010;Davis et al, 2011;Lamkanfi and Kanneganti, 2012).Two studies showed NLRC5 was a positive regulator of type I IFN producing pathway in human fi broblasts and THP-1 cells (Kuenzel et al, 2010;Neerincx et al, 2010). However, NLRC5 was shown to suppress type I IFN production through association with RIG-I and MDA5 (the dsRNA sensors), or inhibit NF-κB pathway through its direct binding with IκB kinase-α (IKK-α) and IKK-β (Cui et al, 2010).…”

Section: Function Of Nlrc5 In Innate Immune Responsementioning

confidence: 99%

“…However, NLRC5 was shown to suppress type I IFN production through association with RIG-I and MDA5 (the dsRNA sensors), or inhibit NF-κB pathway through its direct binding with IκB kinase-α (IKK-α) and IKK-β (Cui et al, 2010). The cause of the discrepancy is probably the differential study conditions.…”

Section: Function Of Nlrc5 In Innate Immune Responsementioning

confidence: 99%

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Expression regulation and function of NLRC5

Yao

Qian

2013

Protein Cell

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The NOD like receptors (NLRs), a class of intracellular receptors that respond to pathogen attack or cellular stress, have gained increasing attention. NLRC5, the largest member of the NLR protein family, has recently been identified as a critical regulator of immune responses. While NLRC5 is constitutively and widely expressed, it can be dramatically induced by interferons during pathogen infections. Both in vitro and in vivo studies have demonstrated that NLRC5 is a specifi c and master regulator of major mistocompatibility complex (MHC) class I genes as well as related genes involved in MHC class I antigen presentation. The expression of MHC class I genes is regulated by NLRC5 in coordination with the RFX components through an enhanceosome-dependent manner. And the involvement of NLRC5 in MHC class I mediated CD8 + T cell activation, proliferation and cytotoxicity is proved to be critical for host defense against intracellular bacterial infections. Nevertheless, the role of NLRC5 in innate immunity remains to be further explored. Here, we review the research advances on the structure, expression regulation and function of NLRC5.

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Section: Expression Of Nlrc5mentioning

confidence: 99%

Section: Expression Of Nlrc5mentioning

confidence: 99%

Section: Structure Of Nlrc5mentioning

confidence: 99%

Section: Function Of Nlrc5 In Innate Immune Responsementioning

confidence: 99%

Section: Function Of Nlrc5 In Innate Immune Responsementioning

confidence: 99%

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Expression regulation and function of NLRC5

Yao

Qian

2013

Protein Cell

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NOD‐Like Receptors

Arnold

Kienes

Sowa

et al. 2018

Encyclopedia of Life Sciences

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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.

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Genes regulated by BCL11B during T‐cell development are enriched for de novo mutations found in schizophrenia patients

Fahey

Donohoe

Broin

et al. 2020

American J of Med Genetics Pt B

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While abnormal neurodevelopment contributes to schizophrenia (SCZ) risk, there is also evidence to support a role for immune dysfunction in SCZ. BCL11B, associated with SCZ in GWAS, is a transcription factor that regulates the differentiation and development of cells in the central nervous and immune systems. Here, we use functional genomics data from studies of BCL11B to investigate the contribution of neuronal and immune processes to SCZ pathophysiology. We identified the gene targets of BCL11B in brain striatal cells (n=223 genes), double negative 4 (DN4) developing T cells (n=114 genes) and double positive (DP) developing T cells (n=518 genes) using an integrated analysis of RNA-seq and ChIP-seq data. No gene-set was enriched for genes containing common variants associated with SCZ but the DP gene-set was enriched for genes containing missense de novo mutations (DNMs; P=0.001) using data from 3,447 SCZ trios. Post-hoc analysis revealed the enrichment to be stronger for DP genes negatively-regulated by BCL11B. Biological processes enriched for genes negatively-regulated by BCL11B in DP gene-set included immune system development and cytokine signaling. These analyses, leveraging a GWAS-identified SCZ risk gene and data on gene expression and transcription factor binding, indicate that DNMs in immune pathways contribute to SCZ risk.

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NLRC5 Negatively Regulates the NF-κB and Type I Interferon Signaling Pathways

Cited by 386 publications

References 42 publications

Expression regulation and function of NLRC5

Expression regulation and function of NLRC5

NOD‐Like Receptors

Genes regulated by BCL11B during T‐cell development are enriched for de novo mutations found in schizophrenia patients

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