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The role of N-glycans in regulatory T cells in autoimmunity

Carneiro, P; Vicente, MM; Leite, MI; Santos, ME; Pinho, SS; Fernandes, Â

Regulatory T cells (Tregs) have a key role in the maintenance of immune tolerance and in the prevention of autoimmunity. Recent studies have shown an association between decreased Treg frequency and a deficient suppressive activity with the development of many autoimmune diseases. Although glycosylation, which consists in the addition of glycans to proteins and lipids on the cell surface, is recognized as a cri...


"Mannose glycans as key players in trained immunity: A novel anti-tumoral catal...

Almeida, P; Alves, I; Fernandes, Â; Lima, C; Freitas, R; Braga, I; Correia, J; Jerónimo, C; Pinho, SS

Cell wall glycans isolated from microorganisms are long known to provoke strong immune responses piloted by innate immune cell populations, including monocytes, in the context of Trained Immunity (TI). However, the contribution of yeast-derived mannan in the reprogramming of monocytes remains ill-defined. Here, we demonstrated that TI is often accompanied by an altered gene expression profile of selected glycan...


Reprogramming CD8+ T-cell Branched N-Glycosylation Limits Exhaustion, Enhancing...

Azevedo, CM; Xie, B; Gunn, WG; Peralta, RM; Dantas, CS; Fernandes-Mendes, H; Joshi, S; Dean, V; Almeida, P; Wilfahrt, D; Mendes, N; Portero, JL

T-cell therapies have transformed cancer treatment. While surface glycans have been shown to play critical roles in regulating T-cell development and function, whether and how the glycome influences T cell–mediated tumor immunity remains an area of active investigation. In this study, we show that the intratumoral T-cell glycome is altered early in human colorectal cancer, with substantial changes in branched N...


T-cell branched glycosylation as a mediator of colitis-associated colorectal ca...

Leite-Gomes, E; Silva, MC; Dias, AM; Fernandes, Â; Faria, G; Nogueira, R; Santos-Pereira, B; Fernandes-Mendes, H; Azevedo, CM; Raposo, J; Portero, JL

Background and Aims: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, established as a risk factor for colorectal cancer (CRC) development. Long-standing inflammation appears to play a central role in colitis-associated colorectal cancer (CAC). However, the molecular mechanism underlying CAC progression is still elusive. Previous evidence showed that levels of b...


Glycans in Trained Immunity: Educators of innate immune memory in homeostasis a...

Almeida, P; Fernandes, Â; Alves, I; Pinho, SS

Trained Immunity is defined as a biological process normally induced by exogenous or endogenous insults that triggers epigenetic and metabolic reprogramming events associated with long-term adaptation of innate immune cells. This trained phenotype confers enhanced responsiveness to subsequent triggers, resulting in an innate immune "memory" effect. Trained Immunity, in the past decade, has revealed important be...


Mannosylated glycans impair normal T-cell development by reprogramming commitme...

Vicente, MM; Alves, I; Fernandes, Â; Dias, AM; Santos-Pereira, B; Pérez-Anton, E; Santos, S; Yang, T; Correia, A; Münster-Kühnel, A; Almeida, ARM

T-cell development ensures the formation of diverse repertoires of T-cell receptors (TCRs) that recognize a variety of antigens. Glycosylation is a major posttranslational modification present in virtually all cells, including T-lymphocytes, that regulates activity/functions. Although these structures are known to be involved in TCR-selection in DP thymocytes, it is unclear how glycans regulate other thymic dev...


Functional genetic variants in atg10 are associated with acute myeloid leukemia

Castro, I; Sampaio-Marques, B; Areias, AC; Sousa, H; Fernandes, Â; Sanchez-Maldonado, JM; Cunha, C; Carvalho, A; Sainz, J; Ludovico, P

Acute myeloid leukemia (AML) is the most common acute leukemia, characterized by a heterogeneous genetic landscape contributing, among others, to the occurrence of metabolic repro-gramming. Autophagy, a key player on metabolism, plays an essential role in AML. Here, we examined the association of three potentially functional genetic polymorphisms in the ATG10 gene, central for the autophagosome formation. We sc...


Glycosylation in cancer: Selected roles in tumour progression, immune modulatio...

Rodrigues, JG; Balmaña, M; Macedo, JA; Poças, J; Fernandes, Â; Freitas-Junior, JCM; Pinho, SS; Gomes, J; Magalhães, A; Gomes, C; Mereiter, S; Reis, CA

Tumour metastasis is the main cause of cancer related deaths. Metastasis is an intricate multi-step process that requires the acquisition of several cancer cell features, including the modulation of tumour cell migration, adhesion, invasion, and immune evasion. Changes in the cellular glycosylation are associated with malignant transformation of cancer cells, tumour progression and ultimately, metastasis format...


Glycans as key checkpoints of T cell activity and function

Pereira, MS; Alves, I; Vicente, M; Campar, A; Silva, MC; Padrão, NA; Pinto, V; Fernandes, Â; Dias, AM; Pinho, SS

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 regulatio...


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