Browsing by Author "Saraiva, Margarida"
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- Comprehensive assessment of environmental fungus-reactive T cells response in hypersensitivity pneumonitis patientsPublication . Santos, Rita F.; Coelho, Andreia L.; Rufo, João C.; Coelho, David; Gonçalves, Melany; Gonçalves, Samuel L.; Cunha, Cristina; Carvalho, Agostinho; Delgado, Luís; Morais, António; Saraiva, Margarida; Novais-Bastos, HélderHypersensitivity pneumonitis (HP) is an interstitial lung disease that results in parenchymal and small airways inflammation and culminates in breathlessness, negatively impacting patient’s quality of life and survival. HP is initiated by an exaggerated immune response triggered by the inhalation of a variety of environmental antigens. The identification of the triggering antigen is a cornerstone of the diagnostic algorithm, and importantly, exposure avoidance ameliorates the clinical outcomes. However, the inciting antigen is not identified in a large proportion of patients. A difficult to identify, but common inciting antigen, is exposure to household fungi.
- IL-10 and Cdc42 modulate astrocyte-mediated microglia activation in methamphetamine-induced neuroinflammationPublication . Silva, Ana Isabel; Socodato, Renato; Pinto, Carolina; Terceiro, Ana Filipa; Canedo, Teresa; Relvas, João Bettencourt; Saraiva, Margarida; Summavielle, TeresaMethamphetamine (Meth) use is known to induce complex neuroinflammatory responses, particularly involving astrocytes and microglia. Building upon our previous research, which demonstrated that Meth stimulates astrocytes to release tumor necrosis factor (TNF) and glutamate, leading to microglial activation, this study investigates the role of the anti-inflammatory cytokine interleukin-10 (IL-10) in this process. Our findings reveal that the presence of recombinant IL-10 (rIL-10) counteracts Meth-induced excessive glutamate release in astrocyte cultures, which significantly reduces microglial activation. This reduction is associated with the modulation of astrocytic intracellular calcium (Ca2+) dynamics, particularly by restricting the release of Ca2+ from the endoplasmic reticulum to the cytoplasm. Furthermore, we identify the small Rho GTPase Cdc42 as a crucial intermediary in the astrocyte-to-microglia communication pathway under Meth exposure. By employing a transgenic mouse model that overexpresses IL-10 (pMT-10), we also demonstrate in vivo that IL-10 prevents Meth-induced neuroinflammation. These findings not only enhance our understanding of Meth-related neuroinflammatory mechanisms, but also suggest IL-10 and Cdc42 as putative therapeutic targets for treating Meth-induced neuroinflammation.
- Unveiling common molecular pathways linked to ILDs with progressive fibrosing phenotype: the role of MUC5BPublication . Santos, Rita F.; Gonçalves, Melany; Mota, Patrícia Caetano; Cardoso, Catarina Gouveia; Coelho, Andreia L.; Sokhatska, Oksana; Beltrão, Marília; Guimarães, Susana; Delgado, Luís; Soares, Miguel; Morais, António; Saraiva, Margarida; Bastos, Hélder NovaisProgressive fibrosing ILDs (PF-ILDs) comprise a heterogeneous group of lung disorders associated with high morbidity and mortality, that exhibit a continuous worsening phenotype despite standard treatment. Among PF-ILDs are pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (HP), involving complex interactions between host genetics and different environmental triggers, shaping the immune milieu that ultimately drives the fibrotic cascade in a susceptible patient. The MUC5B promoter variant rs35705950 is the common genetic variant associated with the greatest risk of developing IPF. As IPF and fibrotic HP present phenotypic resemblances, we aim to analyze the role of rs35705950 MUC5B single nucleotide polymorphism (SNP) in common molecular pathways linked to PF-ILDs. Herein, taking advantage of our extensive ILD patients’ cohort, we found that MUC5B rs35705950 GT and TT genotypes frequency was dramatically increased in IPF and fibrotic HP compared to healthy controls.