Human intestinal epithelial cells respond to β‐glucans via Dectin‐1 and Syk

Cohen-Kedar, Sarit; Baram, Liran; Elad, Hofit; Brazowski, Eli; Guzner-Gur, Hanan; Dotan, Iris

doi:10.1002/eji.201444876

Cited by 92 publications

(107 citation statements)

References 56 publications

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“…S4), consistent with previous studies demonstrating dectin-1 expression by human gut and airway epithelial cells (19, 20). Although nonepithelial structural cells (CD45 − EpCAM − ) in human nasal tissue also express dectin-1, such expression appears to be relatively minimal compared with epithelial cells (fig.…”

Section: Resultssupporting

confidence: 91%

“…Although dectin-1 expression has been primarily associated with antigen-presenting cells (APCs), recent studies have demonstrated that dectin-1 is also expressed by mucosal epithelial cells (19, 20). Moreover, because epithelial cells are a primary source of IL-33 in the lungs (21–25), we ascertained the contribution of Clec7a expression in hematopoietic and nonhematopoietic compartments to allergic airway disease.…”

Section: Resultsmentioning

confidence: 99%

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Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases

et al. 2018

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The key factors underlying the development of allergic diseases—the propensity for a minority of individuals to develop dysfunctional responses to harmless environmental molecules—remain undefined. We report a pathway of immune counter-regulation that suppresses the development of aeroallergy and shrimp-induced anaphylaxis. In mice, signaling through epithelially expressed dectin-1 suppresses the development of type 2 immune responses through inhibition of interleukin-33 (IL-33) secretion and the subsequent recruitment of IL-13–producing innate lymphoid cells. Although this homeostatic pathway is functional in respiratory epithelial cells from healthy humans, it is dramatically impaired in epithelial cells from asthmatic and chronic rhinosinusitis patients, resulting in elevated IL-33 production. Moreover, we identify an association between a single-nucleotide polymorphism (SNP) in the dectin-1 gene loci and reduced pulmonary function in two cohorts of asthmatics. This intronic SNP is a predicted eQTL (expression quantitative trait locus) that is associated with reduced dectin-1 expression in human tissue. We identify invertebrate tropomyosin, a ubiquitous arthropod-derived molecule, as an immunobiologically relevant dectin-1 ligand that normally serves to restrain IL-33 release and dampen type 2 immunity in healthy individuals. However, invertebrate tropomyosin presented in the context of impaired dectin-1 function, as observed in allergic individuals, leads to unrestrained IL-33 secretion and skewing of immune responses toward type 2 immunity. Collectively, we uncover a previously unrecognized mechanism of protection against allergy to a conserved recognition element omnipresent in our environment.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases

et al. 2018

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“…It was also reported that laminarin activates human intestinal epithelial cells to secrete pro-inflammatory chemokines (IL8 and CCL2) (9). Furthermore, Drosophila gram-negative bacteria binding protein-1 (DGNBP-1) can bind to LPS and laminarin to enhance immune-related gene expression (11).…”

Section: Discussionmentioning

confidence: 99%

“…In both adult and larval locusts, the injection of laminarin has been shown to induce immune responses (7,8). It was reported that laminarin activates human intestinal epithelial cells to secrete proinflammatory chemokines such as interleukin-8 (IL8) and chemokine (C-C motif) ligand 2 (CCL2) in adectin-1 and spleen tyrosine kinase (SYK)-dependent manner (9).…”

mentioning

confidence: 99%

Laminarin Promotes Immune Responses and Reduces Lactate Dehydrogenase but Increases Glutamic Pyruvic Transaminase in Normal Mice In Vivo

2018

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Abstract. Background mg treatment. Laminarin did not affect T-cell and B-cell proliferation. Laminarin increased the level of GPT and reduced that of LDH at all doses, indicating laminarin can protect against liver injury. Laminarin is worthy of investigation in future experiments on improving immune responses.It is well documented that the immune system involves sophisticated networks, and is not only responsible for protecting the host against diseases including foreign materials but also protects against toxic substances (1). Therefore, there has been focus on developing immune responses in order to protect against toxic substances entering the human body (2). In particular, many studies have paid attention to improving immune responses in humans from natural products. 523

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“…Expression of dectin-1 was originally thought to be primarily restricted to myeloid cells, including DCs, monocytes, macrophages, and neutrophils, although human B cells and subsets of T cells also express this receptor [1]. More recently, expression of dectin-1 has been described in human mast cells, keratinocytes, and epithelial cells [2-4]. …”

Section: Dectin-1mentioning

confidence: 99%

Antifungal Innate Immunity: A Perspective from the Last 10 Years

Salazar¹,

Brown²

2018

J Innate Immun

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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.

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Human intestinal epithelial cells respond to β‐glucans via Dectin‐1 and Syk

Abstract: Intestinal epithelial cells (IECs

Cited by 92 publications

References 56 publications

Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases

Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases

Laminarin Promotes Immune Responses and Reduces Lactate Dehydrogenase but Increases Glutamic Pyruvic Transaminase in Normal Mice In Vivo

Antifungal Innate Immunity: A Perspective from the Last 10 Years

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