C-type lectin receptors in the control of T helper cell differentiation

Geijtenbeek, Teunis B. H.; Gringhuis, Sonja I.

doi:10.1038/nri.2016.55

Cited by 202 publications

(186 citation statements)

References 129 publications

Supporting

Mentioning

180

Contrasting

Unclassified

Order By: Relevance

“…Therefore, endogenous Mincle ligands may serve as auto-adjuvants, activating the innate immune system. Interestingly, the activation of Mincle by its ligands, such as trehalose-6,6′-dimycolate from M. tuberculosis or the synthetic adjuvant trehalose dibehenate, promotes Th1/Th17 T-cell responses (9,13,37). We found in allergic inflamed ears from Mincle-KO mice a suppressed production of IL-17A, which is regarded as a signature cytokine for Th17 cells (38).…”

Section: Discussionmentioning

confidence: 73%

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

Section: Discussionmentioning

confidence: 73%

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

show abstract

“…Mincle ligands have been reported to induce Th1 or Th17 or both Th1/Th17 responses (7,(60)(61)(62)(63). Although the precise molecular mechanisms underlying different Th responses via the same CLRs are presently unknown, the intensity of signaling through ITAMs may determine the type of responses (63)(64)(65)(66).…”

Section: Discussionmentioning

confidence: 99%

“…Although the precise molecular mechanisms underlying different Th responses via the same CLRs are presently unknown, the intensity of signaling through ITAMs may determine the type of responses (63)(64)(65)(66). Indeed, strong Mincle signaling delivered through plate-coated purified β-GlcCer preferentially induced Th17 responses.…”

Section: Discussionmentioning

confidence: 99%

Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity

Nagata

Izumi

Ishikawa

et al. 2017

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

147

126

View full text Add to dashboard Cite

Sensing and reacting to tissue damage is a fundamental function of immune systems. Macrophage inducible C-type lectin (Mincle) is an activating C-type lectin receptor that senses damaged cells. Notably, Mincle also recognizes glycolipid ligands on pathogens. To elucidate endogenous glycolipids ligands derived from damaged cells, we fractionated supernatants from damaged cells and identified a lipophilic component that activates reporter cells expressing Mincle. Mass spectrometry and NMR spectroscopy identified the component structure as β-glucosylceramide (GlcCer), which is a ubiquitous intracellular metabolite. Synthetic β-GlcCer activated myeloid cells and induced production of inflammatory cytokines; this production was abrogated in Mincle-deficient cells. Sterile inflammation induced by excessive cell death in the thymus was exacerbated by hematopoietic-specific deletion of degrading enzyme of β-GlcCer (β-glucosylceramidase, GBA1). However, this enhanced inflammation was ameliorated in a Mincle-deficient background. GBA1-deficient dendritic cells (DCs) in which β-GlcCer accumulates triggered antigen-specific T-cell responses more efficiently than WT DCs, whereas these responses were compromised in DCs from GBA1 × Mincle double-deficient mice. These results suggest that β-GlcCer is an endogenous ligand for Mincle and possesses immunostimulatory activity.

show abstract

“…DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is a type II transmembrane human receptor whose expression is restricted to myeloid cells, including macrophages and DCs [38]. There are 8 murine homologs of DC-SIGN, known as SIGNR, and all of these are located in a gene cluster within chromosome 8.…”

Section: Dc-specific Intercellular Adhesion Molecule-3-grabbing Noninmentioning

confidence: 99%

Antifungal Innate Immunity: A Perspective from the Last 10 Years

Salazar¹,

Brown²

2018

J Innate Immun

View full text Add to dashboard Cite

Fungal pathogens can rarely cause diseases in immunocompetent individuals. However, commensal and normally nonpathogenic environmental fungi can cause life-threatening infections in immunocompromised individuals. Over the last few decades, there has been a huge increase in the incidence of invasive opportunistic fungal infections along with a worrying increase in antifungal drug resistance. As a consequence, research focused on understanding the molecular and cellular basis of antifungal immunity has expanded tremendously in the last few years. This review will provide an overview of the most exciting recent advances in innate antifungal immunity, discoveries that are helping to pave the way for the development of new strategies that are desperately needed to combat these devastating diseases.

show abstract

C-type lectin receptors in the control of T helper cell differentiation

Cited by 202 publications

References 129 publications

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

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

Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity

Antifungal Innate Immunity: A Perspective from the Last 10 Years

Contact Info

Product

Resources

About