Browsing by Author "Carreño, Leandro J."

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    Gestational hypothyroxinemia causes an inflammatory environment at maternal-fetal tissues and fetal brain with impaired hippocampal dendritic spine maturation in the offspring
    (2025) González-Madrid, Enrique; Rangel-Ramírez, Ma. Andreina; Opazo, María C.; Espinoza Soto, Sebastián Andrés; Elgueta Bustos, Daniela Paz; Cancino Lobos, Gonzalo Ignacio; Mery, Elena; Ardiles, Álvaro O.; Duarte, Luisa F.; Soto, Jorge A.; Carreño, Leandro J.; Simon, Felipe; Bueno Ramírez, Susan Marcela; González Muñoz, Pablo Alberto; Kalergis Parra, Alexis Mikes; Riedel, Claudia A.
    Gestational hypothyroxinemia (HTX) is associated with cognitive impairments and autism traits in offspring. However, the underlying mechanisms remain unclear. Prenatal inflammation impairs cortical development and induces diverse neurodevelopmental outcomes. Since thyroid dysfunction elicits inflammation, we sought to investigate whether HTX triggers prenatal pro-inflammatory responses. Using a mouse model of gestational HTX, we found elevated levels of IL-6 and IL-17 A in maternal serum, placental tissues, and embryonic brains at embryonic day (E)14 compared to euthyroid (EUT) dams. We also found increased proportions of dendritic cells, NK cells, M1-like macrophages, and monocytes in the placental tissues of HTX dams. Furthermore, gestational HTX exposure led to reduced Tbr2⁺ progenitors, increased Tbr1⁺ neurons, and an expanded Iba1⁺ microglial population in HTX-exposed embryos compared to EUT-exposed embryos. At postnatal day (P)55, the offspring gestated under HTX exhibited reduced hippocampal dendritic spine density and maturity compared to the progeny gestated under EUT. Notably, restoring T4 levels during HTX induction (HTX + T4 dams) prevented these alterations during pregnancy and in the offspring of HTX + T4 dams. These findings show that gestational HTX causes inflammation during pregnancy and has neurodevelopmental effects on the progeny, opening new pathways related to how maternal HTX impairs neurodevelopment in the offspring.
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    Induction of Tolerogenic Dendritic Cells by NF-κB Blockade and Fcγ Receptor Modulation
    (2011) Carreño, Leandro J.; Riedel, Claudia A.; Kalergis, Alexis M.
    Autoimmune diseases develop as a result of an unbalanced adaptive immunity that targets self-antigens and causes destruction of healthy host tissues. Maintenance of peripheral immune tolerance to self- antigens is mainly mediated by dendritic cells (DCs), professional antigen-presenting cells that modulate the activation of T cells. Due to their key role as regulators of adaptive immunity, identification of means of enhancing DC tolerogenic capacity and therapeutic potential is a priority goal to reduce autoimmune disease burden in an antigen-specific manner. Our findings suggest novel approaches to enhance DC capacity to induce self-tolerance and reduce the severity of autoimmune disorders. Specifically, we have shown, both in vitro and in vivo, that NF-κB blockade on DCs by andrographolide or rosiglitazone can significantly enhance the tolerogenic capacity of DCs. Furthermore, we have observed that expression ratio of the activating FcγRIII or the inhibitory FcγRIIb is determinant for the tolerogenic potential of DCs. In this chapter, we describe the procedures to produce tolerogenic DCs and explain the potential therapeutic use of two NF-κB inhibitors for the treatment of autoimmune disease models, such as experimental autoimmune encephalomyelitis (EAE) and systemic lupus erythematosus (SLE) in mice. Therefore, our studies support the notion that FcγRs and NF-κB can be considered as pharmacological targets to increase the capacity of DCs to induce or restore self-tolerance and decrease inflammatory damage to self-tissues.
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    Respiratory syncytial virus impairs T cell activation by preventing synapse assembly with dendritic cells
    (2008) González Muñoz, Pablo Alberto; Prado Terrazas, Carolina E.; Leiva, Eduardo D.; Carreño, Leandro J.; Bueno Ramírez, Susan; Riedel, Claudia A.; Kalergis Parra, Alexis Mikes