MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns

Richardson, Mark B.; Williams, Spencer J.

doi:10.3389/fimmu.2014.00288

Cited by 121 publications

(92 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PAMPs are mostly derived from the gut, due to alterations in gut microbiota composition and/or increased intestinal permeability [94]. DAMPs are mostly derived from damaged cells and include HMGB1, adenosine triphosphate (ATP), uric acid, cholesterol crystals, DNA fragments and fatty acids.…”

Section: Key Players In Aldmentioning

confidence: 99%

Key Events Participating in the Pathogenesis of Alcoholic Liver Disease

2017

View full text Add to dashboard Cite

Alcoholic liver disease (ALD) is a leading cause of morbidity and mortality worldwide. It ranges from fatty liver to steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The most prevalent forms of ALD are alcoholic fatty liver, alcoholic hepatitis (AH) and alcoholic cirrhosis, which frequently progress as people continue drinking. ALD refers to a number of symptoms/deficits that contribute to liver injury. These include steatosis, inflammation, fibrosis and cirrhosis, which, when taken together, sequentially or simultaneously lead to significant disease progression. The pathogenesis of ALD, influenced by host and environmental factors, is currently only partially understood. To date, lipopolysaccharide (LPS) translocation from the gut to the portal blood, aging, gender, increased infiltration and activation of neutrophils and bone marrow-derived macrophages along with alcohol plus iron metabolism, with its associated increase in reactive oxygen species (ROS), are all key events contributing to the pathogenesis of ALD. This review aims to introduce the reader to the concept of alcohol-mediated liver damage and the mechanisms driving injury.

show abstract

Section: Key Players In Aldmentioning

confidence: 99%

Key Events Participating in the Pathogenesis of Alcoholic Liver Disease

2017

View full text Add to dashboard Cite

show abstract

“…(5)]. However, recent reports indicate that Mincle rather than purely inducing pro-inflammatory responses is an immune modulator as its engagement also promotes expression of anti-inflammatory cytokines and counter regulates pro-inflammatory signaling pathways (62).…”

Section: Mincle Modulates Inflammatory Responsesmentioning

confidence: 99%

Macrophage Inducible C-Type Lectin As a Multifunctional Player in Immunity

2017

View full text Add to dashboard Cite

The macrophage-inducible C-type lectin (Mincle) is an innate immune receptor on myeloid cells sensing diverse entities including pathogens and damaged cells. Mincle was first described as a receptor for the mycobacterial cell wall glycolipid, trehalose-6,6′-dimycolate, or cord factor, and the mammalian necrotic cell-derived alarmin histone deacetylase complex unit Sin3-associated protein 130. Upon engagement by its ligands, Mincle induces secretion of innate cytokines and other immune mediators modulating inflammation and immunity. Since its discovery more than 25 years ago, the understanding of Mincle’s immune function has made significant advances in recent years. In addition to mediating immune responses to infectious agents, Mincle has been linked to promote tumor progression, autoimmunity, and sterile inflammation; however, further studies are required to completely unravel the complex role of Mincle in these distinct host responses. In this review, we discuss recent findings on Mincle’s biology with an emphasis on its diverse functions in immunity.

show abstract

“…The ligation of Mincle by its ligands leads to the interaction of Mincle with the adaptor protein Fc receptor γ-chain (FcRγ) and the recruitment of spleen tyrosine kinase (Syk) (7,8). The signal is subsequently transmitted to NF-κB via the CARD9-BCL10-MALT1 pathway, leading to the production of a spectrum of proinflammatory cytokines (6,8,9).…”

mentioning

confidence: 99%

“…Mincle (also called Clec4e or Clecsf9) is a type-II transmembrane C-type lectin receptor that recognizes mycobacteria and pathogenic fungi. PAMPs recognized by Mincle are predominantly amphiphilic lipids, such as trehalose-6,6′-dimycolate (TDM) from Mycobacterium tuberculosis and glyceroglycolipids from Malassezia fungi (6). Mincle also recognizes endogenous spliceosome-associated protein 130 (SAP130), which is a constitutively expressed nuclear protein and a subunit of the histone deacetylase complex (7).…”

mentioning

confidence: 99%

Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate

Kostarnoy

Gancheva

Lepenies

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Sterile (noninfected) inflammation underlies the pathogenesis of many widespread diseases, such as allergies and autoimmune diseases. The evolutionarily conserved innate immune system is considered to play a key role in tissue injury recognition and the subsequent development of sterile inflammation; however, the underlying molecular mechanisms are not yet completely understood. Here, we show that cholesterol sulfate, a molecule present in relatively high concentrations in the epithelial layer of barrier tissues, is selectively recognized by Mincle (Clec4e), a C-type lectin receptor of the innate immune system that is strongly up-regulated in response to skin damage. Mincle activation by cholesterol sulfate causes the secretion of a range of proinflammatory mediators, and s.c. injection of cholesterol sulfate results in a Mincle-mediated induction of a severe local inflammatory response. In addition, our study reveals a role of Mincle as a driving component in the pathogenesis of allergic skin inflammation. In a well-established model of allergic contact dermatitis, the absence of Mincle leads to a significant suppression of the magnitude of the skin inflammatory response as assessed by changes in ear thickness, myeloid cell infiltration, and cytokine and chemokine secretion. Taken together, our results provide a deeper understanding of the fundamental mechanisms underlying sterile inflammation.innate immunity | sterile inflammation | allergy | Mincle | cholesterol sulfate

show abstract

MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns

Cited by 121 publications

References 45 publications

Key Events Participating in the Pathogenesis of Alcoholic Liver Disease

Key Events Participating in the Pathogenesis of Alcoholic Liver Disease

Macrophage Inducible C-Type Lectin As a Multifunctional Player in Immunity

Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate

Contact Info

Product

Resources

About