C-Type Lectin Receptor Dectin-2 Binds to an Endogenous Protein β-Glucuronidase on Dendritic Cells

Mori, Daiki; Shibata, Kensuke; Yamasaki, Satoshi

doi:10.1371/journal.pone.0169562

Cited by 17 publications

(7 citation statements)

References 30 publications

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“…22 DECTIN-2 was shown to recognize as "danger sensor" molecules released into DC culture and a putative ligand on regulatory T cells to suppress immune responses. 41,42 An endogenous ligand for DECTIN-1 has also been reported on T cells that, in contrast to CLEC-1, acts as a costimulatory molecule enhancing T-cell proliferation. 43 Therefore, the identification of CLEC-1 ligand(s) is urgently needed to better decipher cell signaling and function.…”

Section: Cd25mentioning

confidence: 99%

Cell-surface C-type lectin-like receptor CLEC-1 dampens dendritic cell activation and downstream Th17 responses

et al. 2017

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Key Points• CLEC-1 is restricted to CD16 2 myeloid DCs in human blood and acts as an inhibitory receptor to restrain downstream Th17 activation.• CLEC-1-deficient rats highlight an in vivo function for CLEC-1 in preventing excessive T-cell priming and effector Th responses.Dendritic cells (DCs) represent essential antigen-presenting cells that are critical for linking innate and adaptive immunity, and influencing T-cell responses. Among pattern recognition receptors, DCs express C-type lectin receptors triggered by both exogenous and endogenous ligands, therefore dictating pathogen response, and also shaping T-cell immunity.We previously described in rat, the expression of the orphan C-type lectin-like receptor-1 (CLEC- 1) by DCs and demonstrated in vitro its inhibitory role in downstream T helper 17 (Th17)activation. In this study, we examined the expression and functionality of CLEC-1 in human DCs, and show a cell-surface expression on the CD16 2 subpopulation of blood DCs and on monocytederived DCs (moDCs). CLEC-1 expression on moDCs is downregulated by inflammatory stimuli and enhanced by transforming growth factor b. Moreover, we demonstrate that CLEC-1 is a functional receptor on human moDCs and that although not modulating the spleen tyrosine kinase-dependent canonical nuclear factor-kB pathway, represses subsequent Th17 responses.Interestingly, a decreased expression of CLEC1A in human lung transplants is predictive of the development of chronic rejection and is associated with a higher level of interleukin 17A (IL17A). Importantly, using CLEC-1-deficient rats, we showed that disruption of CLEC-1 signaling led to an enhanced Il12p40 subunit expression in DCs, and to an exacerbation of downstream in vitro and in vivo CD4 1 Th1 and Th17 responses. Collectively, our results establish a role for CLEC-1 as an inhibitory receptor in DCs able to dampen activation and downstream effector Th responses. As a cell-surface receptor, CLEC-1 may represent a useful therapeutic target for modulating T-cell immune responses in a clinical setting.

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Section: Cd25mentioning

confidence: 99%

Cell-surface C-type lectin-like receptor CLEC-1 dampens dendritic cell activation and downstream Th17 responses

et al. 2017

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“…This approach has already been applied successfully to vaccine design using carbohydrate-based adjuvants ( 22 , 59 , 60 ). Besides CLR–Fc fusion protein libraries, reporter cell lines expressing the respective CLR are used to identify novel CLR–pathogen interactions and CLR ligands ( 61 , 62 ). In addition, such reporter cell lines also allow for investigating if the identified CLR ligands act as potential agonists or antagonists.…”

Section: Discussionmentioning

confidence: 99%

C-Type Lectin Receptor (CLR)–Fc Fusion Proteins As Tools to Screen for Novel CLR/Bacteria Interactions: An Exemplary Study on Preselected Campylobacter jejuni Isolates

et al. 2018

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C-type lectin receptors (CLRs) are carbohydrate-binding receptors that recognize their ligands often in a Ca2+-dependent manner. Upon ligand binding, myeloid CLRs in innate immunity trigger or inhibit a variety of signaling pathways, thus initiating or modulating effector functions such as cytokine production, phagocytosis, and antigen presentation. CLRs bind to various pathogens, including viruses, fungi, parasites, and bacteria. The bacterium Campylobacter jejuni (C. jejuni) is a very frequent Gram-negative zoonotic pathogen of humans, causing severe intestinal symptoms. Interestingly, C. jejuni expresses several glycosylated surface structures, for example, the capsular polysaccharide (CPS), lipooligosaccharide (LOS), and envelope proteins. This “Methods” paper describes applications of CLR–Fc fusion proteins to screen for yet unknown CLR/bacteria interactions using C. jejuni as an example. ELISA-based detection of CLR/bacteria interactions allows a first prescreening that is further confirmed by flow cytometry-based binding analysis and visualized using confocal microscopy. By applying these methods, we identified Dectin-1 as a novel CLR recognizing two selected C. jejuni isolates with different LOS and CPS genotypes. In conclusion, the here-described applications of CLR–Fc fusion proteins represent useful methods to screen for and identify novel CLR/bacteria interactions.

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“…Dectin-2, as demonstrated using a biotin-tagged tetrameric protein, binds to structures with mannose α1-2 and α1,4-linked disaccharides, with higher affinity relative to mannose, due to the reducing end mannose occupying the primary binding site and the non-reducing terminal mannose residue binding in an extended binding site (Feinberg et al, 2017). Other ligands identified using Fc Dectin-2 are the endogenous N-glycosylated ligand β-glucuronidase, requiring the intact EPN motif (Mori et al, 2017), the Blastomyces dermatitidis glycoprotein Eng2, the mannoprotein (MP98) from acapsular C. neoformans Cap67, and bacterial capsular polysaccharides from S. pneumoniae (Table 1).…”

Section: The Group II Clrsmentioning

confidence: 99%

Fc‐conjugated C‐type lectin receptors: Tools for understanding host–pathogen interactions

Willment

2021

Molecular Microbiology

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For ease of purification and a number of other beneficial factors, which will be discussed below, the C-type lectin receptor's (CLR's) ligand-binding domain is generally fused to the hinge region of the human immunoglobulin G1 (IgG1) Fc portion containing the constant heavy (CH) 1 and CH2 domains (Figure 1), which depending on the final application, can have modifications altering the Fc proteins' in vivo effector functions, for example, reduced activation of complement C1q (P331S), decreased binding to mammalian cell

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C-Type Lectin Receptor Dectin-2 Binds to an Endogenous Protein β-Glucuronidase on Dendritic Cells

Cited by 17 publications

References 30 publications

Cell-surface C-type lectin-like receptor CLEC-1 dampens dendritic cell activation and downstream Th17 responses

Cell-surface C-type lectin-like receptor CLEC-1 dampens dendritic cell activation and downstream Th17 responses

C-Type Lectin Receptor (CLR)–Fc Fusion Proteins As Tools to Screen for Novel CLR/Bacteria Interactions: An Exemplary Study on Preselected Campylobacter jejuni Isolates

Fc‐conjugated C‐type lectin receptors: Tools for understanding host–pathogen interactions

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