Browsing by Author "Almeida, Catarina R."
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- Fibrinogen scaffolds with immunomodulatory properties promote in vivo bone regenerationPublication . Vasconcelos, Daniel M.; Gonçalves, Raquel M.; Almeida, Catarina R.; Pereira, Inês O.; Oliveira, Marta I.; Neves, Nuno; Silva, Andreia M.; Ribeiro, António C.; Cunha, Carla; Almeida, Ana R.; Ribeiro, Cristina C.; Gil, Ana M.; Seebach, Elisabeth; Kynast, Katharina L.; Richter, Wiltrud; Lamghari, Meriem; Santos, Susana G.; Barbosa, Mário A.The hypothesis behind this work is that fibrinogen (Fg), classically considered a pro-inflammatory protein, can promote bone repair/regeneration. Injury and biomaterial implantation naturally lead to an inflammatory response, which should be under control, but not necessarily minimized. Herein, porous scaffolds entirely constituted of Fg (Fg-3D) were implanted in a femoral rat bone defect and investigated at two important time points, addressing the bone regenerative process and the local and systemic immune responses, both crucial to elucidate the mechanisms of tissue remodelling. Fg-3D led to early infiltration of granulation tissue (6 days post-implantation), followed by bone defect closure, including periosteum repair (8 weeks post-injury). In the acute inflammatory phase (6 days) local gene expression analysis revealed significant increases of pro-inflammatory cytokines IL-6 and IL-8, when compared with non-operated animals. This correlated with modified proportions of systemic immune cell populations, namely increased T cells and decreased B, NK and NKT lymphocytes and myeloid cell, including the Mac- 1þ (CD18þ/CD11bþ) subpopulation. At 8 weeks, Fg-3D led to decreased plasma levels of IL-1b and increased TGF-b1. Thus, our data supports the hypothesis, establishing a link between bone repair induced by Fg-3D and the immune response. In this sense, Fg-3D scaffolds may be considered immunomodulatory biomaterials.
- Metabolic control of T cell immune response through glycans in inflammatory bowel diseasePublication . Dias, Ana M.; Correia, Alexandra; Pereira, Márcia S.; Almeida, Catarina R.; Alves, Inês; Pinto, Vanda; Catarino, Telmo A.; Mendes, Nuno; Leander, Magdalena; Oliva-Teles, MT; Maia, Luís; Delerue-Matos, Cristina; Taniguchi, Naoyuki; Lima, Margarida; Pedroto, Isabel; Marcos-Pinto, Ricardo; Lago, Paula; Reis, Celso A.; Vilanova, Manuel; Pinho, Salomé S.Mucosal T lymphocytes from patients with ulcerative colitis (UC) were previously shown to display a deficiency in branched N-glycosylation associated with disease severity. However, whether this glycosylation pathway shapes the course of the T cell response constituting a targeted-specific mechanism in UC remains largely unknown. In this study, we demonstrated that metabolic supplementation of ex vivo mucosal T cells from patients with active UC with N-acetylglucosamine (GlcNAc) resulted in enhancement of branched N-glycosylation in the T cell receptor (TCR), leading to suppression of T cell growth, inhibition of the T helper 1 (Th1)/Th17 immune response, and controlled T cell activity. We further demonstrated that mouse models displaying a deficiency in the branched N-glycosylation pathway (MGAT5−/−, MGAT5+/−) exhibited increased susceptibility to severe forms of colitis and early-onset disease. Importantly, the treatment of these mice with GlcNAc reduced disease severity and suppressed disease progression due to a controlled T cell-mediated immune response at the intestinal mucosa. In conclusion, our human ex vivo and preclinical results demonstrate the targeted-specific immunomodulatory properties of this simple glycan, proposing a therapeutic approach for patients with UC.