Aldosterona e IL-17 en la génesis de la hipertensión arterial mineralocorticoídea, un estudio ex vivo / Aldosterone and il-17 in the genesis of mineralocorticoid arterial hypertension: an ex vivo study

Background: Treatment of dendritic cells (DC) with aldosterone induces the secretion of IL-6 and TGF-beta. The polarization of naïve T cells to helper 17 T lymphocytes with DCs pre-incubated with aldosterone, has been described in vivo, generating an IL-17 hyper-secreting phenotype, a cytokine associated with cardiac and renal fibrosis. There are mineralocorticoid receptors (MR) in immune cells and their activation may determine the inflammatory (M1) or adaptive (M2) macrophage phenotype. Aldosterone levels could regulate immunogenic gene expression in these cells, modulating the liberation of specific cytokines. Aim: To assess in humans the association of aldosterone levels and IL-17 with inflammatory markers in peripheral blood mononuclear cells (PBMC). Material and Methods: In blood samples of 176 participants aged 18 to 67 years (61 percent women) with a body mass index of 27.1 +/- 4.8 kg/m2, aldosterone, plasma renin activity (ARP), cortisol, C reactive protein, andIL-17 were measured. mRNA was isolated from PBMCs to measure the expression of MR RAC-1, HO-1, TLR-4, CD-14, NGAL and IL-17 by real time polymerase chain reaction. Results: Aldosterone correlated positively with ARP and the expression of CD-14 in PBMCs. Plasma levels of IL-17 were positively associated with the expression of MR, Rac1a and NGAL. Conclusions: Aldosterone and IL-17 levels were associated with inflammatory activation markers in PBMC, which could activate MRand promote a subclinical inflammatory status inducing hypertension.

Células dendríticas como determinantes del equilibrio entre inmunidad y autoinmunidad / Dendritic cells like determinants of the balance between immunity and autoimmunity

Autoinmune diseases occur when the immunological system loses its capability to recognize between self and foreign, and develops a response against healthy tissues. Both molecular bases that trigger these pathologies and genetic factors of susceptibility are unknown. Identification of these factors is fundamental for understanding and developing specific therapies for autoimmune diseases. Dendritic cells (DCs) - professional antigen presenting cells - play a fundamental roll in the development and modulation of the acquired immune response because they have the unique capacity to active naïve T lymphocytes. In order to activate T lymphocytes, the DCs must supply simultaneously two molecular signals which correspond to the antigen (or peptid complex MHC) plus costimulating signals. In absence of costimulation, the DCs induce inactivation of T lymphocytes, mechanism by which they are able to maintain peripheral tolerance against self antigens. In this way, it has been proposed that the immature DCs present antigens in absence of costimulation and provoke tolerance. On the contrary, mature DCs present antigens together with costimulating signals, which lead to immunity. In self-immune diseases, the process of tolerance in the presence of autoantigens could be deficient due to alterations in the normal function of DCs. One of the causes of this defect could be that there is an unbalance in the expression of activating and inhibiting Fcy receptors on the surface of DCs. This would generate DCs with a constitutive phenotype of maturity that would interfere with its tolerogenic activity, and would favor the permanent activation of T lymphocytes, including those that are autoreactive.

La detección antígeno-específica de linfocitos T y sus aplicaciones clínicas / Clinical applications of antigen-specific detection of T lymphocytes

The important role that T lymphocytes play during the immune response against pathogens and tumor cells has encouraged the development of technologies aimed to detect these immune cells in an antigen-specific fashion. Recently, a methodology consisting of the production of soluble ligands that bind the T lymphocyte receptor was developed. Such ligands consist of molecules from the Major Histocompatibility Complex loaded with either pathogen or tumor derived peptides. These molecular complexes are tetramerized to enhance the binding efficiency to the T cell receptor (TCR), which improves the detection sensitivity of antigen specific T lymphocytes. This new technology is currently used successfully during the follow up patients that were vaccinated against certain tumor antigens, to evaluate the expansion of tumor specific T lymphocytes. This methodology is also promising for the detection and specific deletion of autoreactive T lymphocytes as a treatment for autoimmune disorders. In this article we review the molecular components involved in antigen recognition by T lymphocytes, and the potential benefits for Biomedicine that could result from the detection of these cells by soluble specific ligands (Rev MÚd Chile 2004; 132: 371-80).