Browsing by Author "Funes, Samanta C."

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    Contribution of Dysregulated DNA Methylation to Autoimmunity
    (2021) Funes, Samanta C.; Fernández Fierro, Ayleen; Rebolledo Zelada, Diego; Mackern Oberti, Juan P.; Kalergis, Alexis M.
    Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs are known regulators of gene expression and genomic stability in cell growth, development, and differentiation. Because epigenetic mechanisms can regulate several immune system elements, epigenetic alterations have been found in several autoimmune diseases. The purpose of this review is to discuss the epigenetic modifications, mainly DNA methylation, involved in autoimmune diseases in which T cells play a significant role. For example, Rheumatoid Arthritis and Systemic Lupus Erythematosus display differential gene methylation, mostly hypomethylated 5′-C-phosphate-G-3′ (CpG) sites that may associate with disease activity. However, a clear association between DNA methylation, gene expression, and disease pathogenesis must be demonstrated. A better understanding of the impact of epigenetic modifications on the onset of autoimmunity will contribute to the design of novel therapeutic approaches for these diseases.
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    Female offspring gestated in hypothyroxinemia and infected with human Metapneumovirus (hMPV) suffer a more severe infection and have a higher number of activated CD8+ T lymphocytes
    (2022) Funes, Samanta C.; Rios, Mariana; Fernandez-Fierro, Ayleen; Rivera-Perez, Daniela; Soto, Jorge A.; Valbuena, Jose R.; Altamirano-Lagos, Maria J.; Gomez-Santander, Felipe; Jara, Evelyn L.; Zoroquiain, Pablo; Roa, Juan C.; Kalergis, Alexis M.; Riedel, Claudia A.
    Maternal thyroid hormones (THs) are essential for the appropriate development of the fetus and especially for the brain. Recently, some studies have shown that THs deficiency can also alter the immune system development of the progeny and their ability to mount an appropriate response against infectious agents. In this study, we evaluated whether adult mice gestated under hypothyroxinemia (Hpx) showed an altered immune response against infection with human metapneumovirus (hMPV). We observed that female mice gestated under Hpx showed higher clinical scores after seven days of hMPV infection. Besides, males gestated under Hpx have higher lung viral loads at day seven post-infection. Furthermore, the female offspring gestated in Hpx have already reduced the viral load at day seven and accordingly showed an increased proportion of activated (CD71(+) and FasL(+)) CD8(+) T cells in the lungs, which correlated with a trend for a higher histopathological clinical score. These results support that T-4 deficiency during gestation might condition the offspring differently in males and females, enhancing their ability to respond to hMPV.
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    Immune checkpoints and the regulation of tolerogenicity in dendritic cells: Implications for autoimmunity and immunotherapy.
    (2019) Funes, Samanta C.; Manrique de Lara, Amaranta; Altamirano-Lagos, María J.; Mackern-Oberti, Juan P.; Escobar-Vera, Jorge; Kalergis, Alexis M.
    The immune system is responsible for defending the host from a large variety of potential pathogens, while simultaneously avoiding immune reactivity towards self-components. Self-tolerance has to be tightly maintained throughout several central and peripheral processes; immune checkpoints are imperative for regulating the immunity/tolerance balance. Dendritic cells (DCs) are specialized cells that capture antigens, and either activate or inhibit antigen-specific T cells. Therefore, they play a key role at inducing and maintaining immune tolerance. DCs that suppress the immune response have been called tolerogenic dendritic cells (tolDCs). Given their potential as a therapy to prevent transplant rejection and autoimmune damage, several strategies are under development to generate tolDCs, in order to avoid activation and expansion of self-reactive T cells. In this article, we summarize the current knowledge relative to the main features of tolDCs, their mechanisms of action and their therapeutic use for autoimmune diseases. Based on the literature reviewed, autologous antigen-specific tolDCs might constitute a promising strategy to suppress autoreactive T cells and reduce detrimental inflammatory processes.
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    Implications of macrophage polarization in autoimmunity
    (2018) Funes, Samanta C.; Ríos, Mariana; Escobar‐Vera, Jorge; Kalergis Parra, Alexis Mikes
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    Partial long-term clinical improvement after a BCG challenge in systemic lupus erythematosus-prone mice
    (2024) Mora, Valentina P.; Quero, Francisco B.; Troncoso-Bravo, Tays; Orellana, Claudia; Pereira, Patricia; Mackern-Oberti, Juan P.; Funes, Samanta C.; Soto, Jorge A.; Bohmwald, Karen; Bueno, Susan M.; Kalergis, Alexis M.
    Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that causes a breakdown of immune tolerance. Current treatments mainly involve general immunosuppression, increasing the risk of infections. On the other hand, Bacillus Calmette-Gu & eacute;rin (BCG) has been investigated as a potential therapy for autoimmune diseases in recent years, prompting an ongoing investigation. This study aimed to evaluate the effect of BCG vaccination on early and late clinical presentation of SLE in a murine disease model. MRL/MPJ-Faslpr mice were immunized with BCG or treated with PBS as a control. The progress of the disease was evaluated at 27 days post-immunization (dpi) (early) and 56 dpi (late). Clinical parameters and proteinuria were monitored. Blood samples were collected for measurement of antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), and cytokine determination was performed using ELISA. Samples collected from mice were analyzed by flow cytometry and histopathology. We observed a clinical improvement in BCG-treated mice, reduced proteinuria in the latter stages of the disease, and decreased TNF-alpha. However, BCG did not elicit significant changes in ANAs, anti-dsDNA, histopathological scores, or immune cell infiltration. BCG was only partially beneficial in an SLE mouse model, and further research is needed to determine whether the immunity induced by this vaccine can counteract lupus's autoimmune response.