Browsing by Autor "Fernando Figueroa"

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Aldosterone Promotes Autoimmune Damage by Enhancing Th17-Mediated Immunity
(American Association of Immunologists, 2009) Andrés A. Herrada; Francisco Contreras; Natacha P Marini; Cristián A. Amador; Pablo A. González; Claudia Cortés; Claudia A. Riedel; Cristián A. Carvajal; Fernando Figueroa; Luis Michea
Excessive production of aldosterone leads to the development of hypertension and cardiovascular disease by generating an inflammatory state that can be promoted by T cell immunity. Because nature and intensity of T cell responses is controlled by dendritic cells (DCs), it is important to evaluate whether the function of these cells can be modulated by aldosterone. In this study we show that aldosterone augmented the activation of CD8(+) T cells in a DC-dependent fashion. Consistently, the mineralocorticoid receptor was expressed by DCs, which showed activation of MAPK pathway and secreted IL-6 and TGF-beta in response to aldosterone. In addition, DCs stimulated with aldosterone impose a Th17 phenotype to CD4(+) T cells, which have recently been associated with the promotion of inflammatory and autoimmune diseases. Accordingly, we observed that aldosterone enhances the progression of experimental autoimmune encephalomyelitis, an autoimmune disease promoted by Th17 cells. In addition, blockade of the mineralocorticoid receptor prevented all aldosterone effects on DCs and attenuated experimental autoimmune encephalomyelitis development in aldosterone-treated mice. Our data suggest that modulation of DC function by aldosterone enhances CD8(+) T cell activation and promotes Th17-polarized immune responses, which might contribute to the inflammatory damage leading to hypertension and cardiovascular disease.
Evolución del compromiso cardiovascular de pacientes insuficientes renales, en hemodiálisis, sin bloqueo del eje renina-angiotensina
(Q16635223, 2009) S Kunstmann; Antonio Vukusich; Luis Michea; Cristián Varela; I. L. C. De Allende; Sebastián Bravo; Daniela Gainza; Daniela Sepúlveda; Elisa T. Marusic; Fernando Figueroa
Non diabetic patients on chronic hemodialysis have a high frequency of ventricular hypertrophy, carotid media thickening, aortic calcifications and an increase in proinflammatory cytokines.
IL17/IL17RA as a Novel Signaling Axis Driving Mesenchymal Stem Cell Therapeutic Function in Experimental Autoimmune Encephalomyelitis
(Frontiers Media, 2018) Mónica Kurte; Patricia Luz‐Crawford; Ana María Vega-Letter; Rafaël Contreras; Gautier Téjédor; Roberto Elizondo‐Vega; Luna Martinez-Viola; Catalina Fernández-O’Ryan; Fernando Figueroa; Christian Jørgensen
The therapeutic effect of mesenchymal stem cells (MSCs) in multiple sclerosis (MS) and the experimental autoimmune encephalomyelitis (EAE) model has been well described. This effect is, in part, mediated through the inhibition of IL17-producing cells and the generation of regulatory T cells. While proinflammatory cytokines such as IFNγ, TNFα, and IL1β have been shown to enhance MSCs immunosuppressive function, the role of IL17 remains poorly elucidated. The aim of this study was, therefore, to investigate the role of the IL17/IL17R pathway on MSCs immunoregulatory effects focusing on Th17 cell generation in vitro and on Th17-mediated EAE pathogenesis in vivo. In vitro, we showed that the immunosuppressive effect of MSCs on Th17 cell proliferation and differentiation is partially dependent on IL17RA expression. This was associated with a reduced expression level of MSCs immunosuppressive mediators such as VCAM1, ICAM1, and PD-L1 in IL17RA-/- MSCs as compared to wild-type (WT) MSCs. In the EAE model, we demonstrated that while WT MSCs significantly reduced the clinical scores of the disease, IL17RA-/- MSCs injected mice exhibited a clinical worsening of the disease. The disability of IL17RA-/- MSCs to reduce the progression of the disease paralleled the inability of these cells to reduce the frequency of Th17 cells in the draining lymph node of the mice as compared to WT MSCs. Moreover, we showed that the therapeutic effect of MSCs was correlated with the generation of classical Treg bearing the CD4+CD25+Foxp3+ signature in an IL17RA-dependent manner. Our findings reveal a novel role of IL17RA on MSCs immunosuppressive and therapeutic potential in EAE and suggest that the modulation of IL17RA in MSCs could represent a novel method to enhance their therapeutic effect in MS.