Aldosterone Promotes Autoimmune Damage by Enhancing Th17-Mediated Immunity

• Published in: The Journal of immunology (1950) 2010-01, Vol.184 (1), p.191-202
• Main Authors: Herrada, Andres A, Contreras, Francisco J, Marini, Natacha P, Amador, Cristian A, Gonzalez, Pablo A, Cortes, Claudia M, Riedel, Claudia A, Carvajal, Cristian A, Figueroa, Fernando, Michea, Luis F, Fardella, Carlos E, Kalergis, Alexis M
• Format: Article
• Language: English
• Subjects: Aldosterone - immunology; Animals; Autoimmunity; Blotting, Western; CD8-Positive T-Lymphocytes - immunology; Dendritic Cells - immunology; Encephalomyelitis, Autoimmune, Experimental - immunology; Female; Interleukin-17 - immunology; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Mitogen-Activated Protein Kinases - immunology; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - immunology; T-Lymphocyte Subsets - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0802886

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.