Glycans as critical regulators of gut immunity in homeostasis and disease

Dias, Adelaide; Pereira, Márcia S.; Padrão, Nuno A.; Alves, Inês; Marcos-Pinto, Ricardo; Lago, Paula; Pinho, Salomé S.

doi:10.1016/j.cellimm.2018.07.007

Cited by 30 publications

(22 citation statements)

References 164 publications

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“…8,27,[29][30][31] Alterations in these processes can lead to autoimmune diseases and cancer. 5,32 It is not clear whether alterations in cell glycosylation profiles occur as an early event (inducing) or late event (accelerating) in intestinal inflammation. Intestinal T cells from patients with IBD have glycome profiles that differ from those individuals without IBD, characterized by decreased levels of branched N-glycans 19,30 and increased levels of core fucosylation (the addition of a fucose residue to the core structure of N-linked glycans with an a1,6 linkage).…”

Section: Glycosylation In T Cellsmentioning

confidence: 99%

“…61,62 Accordingly, mice models lacking core 1 and core 3derived mucin type O-glycans develop spontaneous colitisassociated cancer. 32,63 Overexpression of b1,6 branching N-glycosylation has been associated with malignancy, 64 cell invasiveness, 18,[65][66][67] and reduced survival times of patients with cancer 68 ( Figure 1). Aberrant expression of branched glycans can affect regulation of immune response, although little is known about its effects in patients with IBD-associated CRC.…”

Section: Glycosylation Alterations In Inflammation-associated Gastroimentioning

confidence: 99%

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Protein Glycosylation as a Diagnostic and Prognostic Marker of Chronic Inflammatory Gastrointestinal and Liver Diseases

et al. 2020

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Glycans are sequences of carbohydrates that are added to proteins or lipids to modulate their structure and function. Glycans modify proteins required for regulation of immune cells, and alterations have been associated with inflammatory conditions. For example, specific glycans regulate T-cell activation, structures, and functions of immunoglobulins; interactions between microbes and immune and epithelial cells; and malignant transformation in the intestine and liver. We review the effects of protein glycosylation in regulation of gastrointestinal and liver functions, and how alterations in glycosylation serve as diagnostic or prognostic factors, or as targets for therapy.

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Section: Glycosylation In T Cellsmentioning

confidence: 99%

Section: Glycosylation Alterations In Inflammation-associated Gastroimentioning

confidence: 99%

Protein Glycosylation as a Diagnostic and Prognostic Marker of Chronic Inflammatory Gastrointestinal and Liver Diseases

et al. 2020

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“…Additionally, glycans can also restrict nonspecific protein-protein interactions, like aggregation of TCRs on the membrane, helping to orient the interactions of the proteins in the central clusters ( 31 ). Demetriou et al demonstrated that β1,6-GlcNAc branched N- glycans structures (catalyzed by GnT-V) regulate T cell activity, namely in CD4 + T cells by increasing the threshold of T cell activation, suppressing T cell growth and signaling ( 30 , 42 ). Moreover, core-fucosylation, which refers to fucose attached to the innermost N- acetylglucosamine of N- linked glycans, catalyzed by α1-6 fucosyltransferase (FUT8), was also shown to affect T cell activity in immune mediated disorders ( 42 , 43 ).…”

Section: Glycans In the Regulation Of T Cell Activity And Functionsmentioning

confidence: 99%

Glycans as Key Checkpoints of T Cell Activity and Function

et al. 2018

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The immune system is highly controlled and fine-tuned by glycosylation, through the addition of a diversity of carbohydrates structures (glycans) to virtually all immune cell receptors. Despite a relative backlog in understanding the importance of glycans in the immune system, due to its inherent complexity, remarkable findings have been highlighting the essential contributions of glycosylation in the regulation of both innate and adaptive immune responses with important implications in the pathogenesis of major diseases such as autoimmunity and cancer. Glycans are implicated in fundamental cellular and molecular processes that regulate both stimulatory and inhibitory immune pathways. Besides being actively involved in pathogen recognition through interaction with glycan-binding proteins (such as C-type lectins), glycans have been also shown to regulate key pathophysiological steps within T cell biology such as T cell development and thymocyte selection; T cell activity and signaling as well as T cell differentiation and proliferation. These effects of glycans in T cells functions highlight their importance as determinants of either self-tolerance or T cell hyper-responsiveness which ultimately might be implicated in the creation of tolerogenic pathways in cancer or loss of immunological tolerance in autoimmunity. This review discusses how specific glycans (with a focus on N-linked glycans) act as regulators of T cell biology and their implications in disease.

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“…Glycans are a source of carbon for microbes, and are crucial to recognition, signalling, and epigenetic regulation between host cells and microbes, which implicates them in a range of immunological and metabolic disorders [5]. Developing interventions and therapeutics that target glycan expression by hosts or microbes is complicated by their diversity and complexity, and hindered by a poor understanding of structure function specificity of both glycan motifs and enzyme cohorts employed by microbes [6,7].…”

Section: Glycans: Sources Structures and Functionsmentioning

confidence: 99%

Glycan Utilisation and Function in the Microbiome of Weaning Infants

et al. 2019

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Glycans are present exogenously in the diet, expressed and secreted endogenously by host cells, and produced by microbes. All of these processes result in them being available to the gut microbiome, firmly placing glycans at the interface of diet–microbe–host interactions. The most dramatic shift in dietary sources of glycans occurs during the transition from the milk-based neonatal diet to the diverse omnivorous adult diet, and this has profound effects on the composition of the gut microbiome, gene expression by microbes and host cells, mucin composition, and immune development from innate towards adaptive responses. Understanding the glycan-mediated interactions occurring during this transitional window may inform dietary recommendations to support gut and immune development during a vulnerable age. This review aims to summarise the current state of knowledge on dietary glycan mediated changes that may occur in the infant gut microbiome and immune system during weaning.

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Glycans as critical regulators of gut immunity in homeostasis and disease

Cited by 30 publications

References 164 publications

Protein Glycosylation as a Diagnostic and Prognostic Marker of Chronic Inflammatory Gastrointestinal and Liver Diseases

Protein Glycosylation as a Diagnostic and Prognostic Marker of Chronic Inflammatory Gastrointestinal and Liver Diseases

Glycans as Key Checkpoints of T Cell Activity and Function

Glycan Utilisation and Function in the Microbiome of Weaning Infants

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