NLRC5 Deficiency Selectively Impairs MHC Class I- Dependent Lymphocyte Killing by Cytotoxic T Cells

Staehli, Francesco; Ludigs, Kristina; Heinz, Leonhard X.; Seguín-Estévez, Queralt; Ferrero, Isabel; Braun, Michel Y; Schroder, Kate; Rebsamen, Manuele; Tardivel, Aubry; Mattmann, Chantal; MacDonald, H. Robson; Romero, Pedro; Reith, Walter; Guarda, Greta; Tschopp, Jürg

doi:10.4049/jimmunol.1102671

Cited by 122 publications

(191 citation statements)

References 42 publications

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“…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. Indeed, this hypothesis is demonstrated in innate immune cells like macrophages (Staehli et al, 2012). Consistent with that, the induction of NLRC5 expression by LPS was abrogated in Ifnαr1 -/-bone marrow-derived macrophages (Staehli et al, 2012).…”

Section: Expression Of Nlrc5supporting

confidence: 72%

“…Indeed, this hypothesis is demonstrated in innate immune cells like macrophages (Staehli et al, 2012). Consistent with that, the induction of NLRC5 expression by LPS was abrogated in Ifnαr1 -/-bone marrow-derived macrophages (Staehli et al, 2012). NLRC5 promoter region is predicted to have STAT1 and NF-κB binding sites (Kuenzel et al, 2010).…”

Section: Expression Of Nlrc5supporting

confidence: 58%

“…While NLRC5 is constitutively expressed in many immune cells, it can also be dramatically induced by a variety of stimulations. 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).…”

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%

“…Likewise, NLRC5 also has bipartite NLS in its N terminus and overexpressed NLRC5 was found to be dominantly localized in the nucleus, suggesting a role of NLRC5 in the nuclear (Meissner et al, 2012a). As a matter of fact, endogenous NLRC5 protein was found to be in both cytoplasmic and nuclear while it was mainly localized in the nucleus after treatment with LepB, an inhibitor of protein nucleus export, suggesting NLRC5 is a cytoplasm-nuclear shuttle protein (Neerincx et al, 2012;Staehli et al, 2012). The results of our structural analyses obtained from Ensembl database have predicted 10 protein coding isoforms of NLRC5 (data not shown).…”

Section: Introductionmentioning

confidence: 98%

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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 Nlrc5supporting

confidence: 72%

Section: Expression Of Nlrc5supporting

confidence: 58%

Section: Expression Of Nlrc5mentioning

confidence: 99%

Section: Expression Of Nlrc5mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Expression regulation and function of NLRC5

Yao

Qian

2013

Protein Cell

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Major Histocompatibility Complex ( MHC ): Mouse

Stuart

2015

Encyclopedia of Life Sciences

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The major histocompatibility complex (MHC) of the mouse, which is called the H2 complex, is located on chromosome 17. It contains genes critical to the functioning of the immune system, the products of which are intimately involved in the initiation of immune responses. The proteins made by these genes display a significant amount of polymorphism, or sequence variability. Few genes possess this degree of polymorphism, but it is critical to the immune response and to the survival of a species. The chief characteristic of MHC molecules is their ability to bind small peptides. These bound peptides along with specific areas of the MHC molecule are the structures that interact with the T‐cell receptor (TCR) leading to activation of a T‐cell immune response, which in turn can active other cells of immune system. Thus, they determine which TCRs are functional which in turn indicates which peptides a T cell will respond to. Key Concepts The historical background and the genetics of MHC development are described. The expression and function of MHC class I genes is described. MHC class I molecules are expressed on virtually all nucleated cells and function to present foreign and self‐antigens to the immune system. MHC class I expression is dependent on peptide binding in the peptide binding groove of the molecule. MHC class I polymorphism is important for species resistance to infectious disease. The expression and function of MHC class II genes is described. MHC class II expression is required for generation and function of CD4 T cells. Nonclassical class I molecules bind a variety of peptide and nonpeptide antigens that are commonly expressed by pathogenic organisms. . The function of other genes found within the H2 complex is described.

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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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NLRC5 Deficiency Selectively Impairs MHC Class I- Dependent Lymphocyte Killing by Cytotoxic T Cells

Cited by 122 publications

References 42 publications

Expression regulation and function of NLRC5

Expression regulation and function of NLRC5

Major Histocompatibility Complex ( MHC ): Mouse

NOD ‐Like Receptors

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