C-type lectins in immunity: recent developments

Dambuza, Ivy M.; Brown, Gordon D.

doi:10.1016/j.coi.2014.12.002

Cited by 407 publications

(323 citation statements)

References 73 publications

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“…Therefore, Nrf2 seems to regulate glycosylation-related gene expression involved in AQP2 trafficking. Indeed, we found upregulated expression of Clec4d and Clec4n genes (69), which encode members of the C-type lectin family (74). This suggests that Clec4d and Clec4n enhance the transport of AQP2 to the apical membrane, thereby enhancing the urinary excretion of AQP2 (69).…”

Section: Novel Function Of Nrf2mentioning

confidence: 93%

Stress-sensing mechanisms and the physiological roles of the Keap1–Nrf2 system during cellular stress

Suzuki

Yamamoto

2017

Journal of Biological Chemistry

344

272

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Edited by Ruma BanerjeeTranscription factor Nrf2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. Nrf2 induces the expression of detoxification and antioxidant enzymes and suppresses the induction of pro-inflammatory cytokine genes. Keap1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of Cullin 3-based E3 ubiquitin ligase. Keap1 regulates the activity of Nrf2 and acts as a sensor for oxidative and electrophilic stresses. In this review, we discuss the molecular mechanisms by which the Keap1-Nrf2 system senses and regulates the cellular response to environmental stresses. In particular, we focus on the multiple stress-sensing mechanisms of Keap1 and novel regulatory functions of Nrf2.Our body is equipped with a defense system that up-regulates the expression levels of cytoprotective enzyme genes. Nrf2 is the central player in the inducible expression of cellular defense enzymes (1, 2). Nrf2 belongs to the CNC (cap-n-collar) subfamily of basic region-leucine zipper-type transcription factors (3). Nrf2 dimerizes with one of the small Maf proteins (sMaf). The Nrf2-sMaf heterodimer binds to the antioxidantresponse element (ARE) 2 or electrophile-response element located in the regulatory regions of many cytoprotective enzyme genes (1, 4 -6). In this way, Nrf2 activates a wide range of cellular defense processes, thereby eliminating harmful substances.Keap1 acts as an E3 ubiquitin ligase substrate-recognition subunit and specifically targets Nrf2 (7-10). In the absence of stress, Nrf2 is efficiently ubiquitinated by the Keap1-Cul3 E3 ligase and degraded rapidly through the proteasome pathway, such that cellular Nrf2 activity is constitutively suppressed. Upon exposure to oxidative or electrophilic stresses, Keap1 loses its ability to ubiquitinate Nrf2, allowing Nrf2 to accumulate in the nucleus and activate its target genes.Recent studies expanded our knowledge on the targets of the Keap1-Nrf2 system, and the molecular mechanisms underpinning how this system senses a variety of environmental stresses. Keap1 primarily regulates Nrf2 in the cytoplasm; however, a Keap1-independent mechanism utilizing ␤-TrCP (␤-transducin repeat-containing protein) in the nucleus also operates (11). Anti-inflammation by Nrf2Several hundred Nrf2 target genes have been identified through gene expression profiling analysis and chromatin immunoprecipitation (ChIP) analysis (12-17). The Nrf2 target genes identified in these studies include enzymes involved in detoxification, anti-oxidation, and metabolism, as summarized in Fig. 1 (18).In addition to protecting against oxidative and xenobiotic insults, Nrf2 has also been known to attenuate inflammation (19). Nrf2 deficiency exacerbates inflammation, such as sepsis, pleurisy, and emphysema, in a variety of murine models (20 -22). In human clinical studies, the Nrf2 inducer Tecfidera (dimethyl fumarate) has been approved for the treatment of multiple sclerosis (23, 24)-at least in part based on its antiinflammatory function. Thus, N...

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Section: Novel Function Of Nrf2mentioning

confidence: 93%

Stress-sensing mechanisms and the physiological roles of the Keap1–Nrf2 system during cellular stress

Suzuki

Yamamoto

2017

Journal of Biological Chemistry

344

272

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“…Autoimmune diseases are a serious public health problems [33] and there is increasing evidence that C-type lectins and complement system are involved in the pathogenesis of the autoimmune diseases [34][35][36][37][38]. We introduced the new systemic clearance mechanism of radiation-induced apoptotic cells, in which SIGN-R1 could initiate and enhance the clearance of apoptotic cells by activating the complement deposition pathway against apoptotic cells in the spleen, integrating the role of SIGN-R1 and complements in the clearance of radiationinduced apoptotic cells.…”

Section: Resultsmentioning

confidence: 99%

Systemic Clearance of Radiation-Induced Apoptotic Cells by SIGN-R1 and Complement Factors and their Involvement in Autoimmune Diseases

Loh¹,

Park²

2015

J Mol Biomark Diagn

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“…CLRs are composed of more than 1,000 proteins that recognize a diverse range of pathogens (parasites, fungi, bacteria and viruses), and are characterized by the presence of at least one C-type lectin-like domain (CTLD) [52]. Of particular interest are the single CTLD-containing extracellular receptors of dectin-1 and dectin-2 clusters which associate with signaling adaptor or possess integral intracellular signaling domains.…”

Section: C-type Lectin-like Receptors (Clrs)mentioning

confidence: 99%

Immune Recognition in Lung Diseases: Basic Research and Clinical Application

Alvarado¹,

Arce²

2016

Clin Infect Immun

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Respiratory diseases are among the leading causes of morbidity and mortality in the world population. Our understanding of the molecular mechanisms leading to recognition of infectious pathogens and harmful endogenous signals by the innate immune system and the adaptive immune system has improved significantly in recent decades. There is increased evidence of the key role of the immune system with its pattern recognition receptors (PRRs) in infectious and non-infectious lung diseases. The PRRs are a family of sensors able to sense different microbial molecules as well as endogenous molecules which are released by the host tissue damage. The commitment of PRRs is a prerequisite for the initiation of immune and inflammatory response to infection and tissue injury that may be beneficial or harmful. The PRRs are germ-line encoded, evolutionarily conserved molecules and consist of Toll-like receptors, NOD-like receptors, RIG-I-like receptors, C-type lectin-like receptors and cytosolic DNA sensors. This review summarizes the prominent role of transmembrane and cytosolic PRRs in the pathogenesis of infectious and non-infectious lung diseases. The PRRs and their signals represent promising targets for prophylactic and therapeutic strategies in various lung diseases.

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C-type lectins in immunity: recent developments

Abstract: HighlightsCLRs play an essential role in immunity to fungi and mycobacteria.CLRs are involved in the regulation of homeostasis, autoimmunity and allergy.CLRs recognise and trigger cellular responses to dead and cancerous cells.

Cited by 407 publications

References 73 publications

Stress-sensing mechanisms and the physiological roles of the Keap1–Nrf2 system during cellular stress

Stress-sensing mechanisms and the physiological roles of the Keap1–Nrf2 system during cellular stress

Systemic Clearance of Radiation-Induced Apoptotic Cells by SIGN-R1 and Complement Factors and their Involvement in Autoimmune Diseases

Immune Recognition in Lung Diseases: Basic Research and Clinical Application

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