Unraveling the immune function of mineralocorticoid receptor (MR) and aldosterone in murine models

Inflammation is a physiological response that could be triggered by endogenous and exogenous stimulus. During inflammation the response is auto limited and regulated to keep homeostasis, because uncontrolled response could lead to death. Inflammatory response is complex and involves many systems which crosstalk each with other. In this line, hormones and its cognate receptors have been described as modulators of immune response. Aldosterone is an adrenal hormone, that controls renal excretion of water and electrolytes to keep blood pressure. This hormone acts through mineralocorticoid receptor (MR) which is a ligand dependent transcription factor mainly expressed in kidneys epithelial cells. However, MR is also expressed in cells of the immune system, adipose tissue, liver and brain, indicating that could be paying a role in these tissues.

Aimed to describe the immunological role of aldosterone-MR, we used a MR conditional knockout mice (MyMRKO). Here we described that aldosterone through MR are involved in toll-like receptor 4 (Tlr4) expression.

This result affected the capacity of MyMRKO dendritic cells (DCs) to sense and responds to its ligand lipopolysaccharide, also failed to induced a proinflammatory prone phenotype. These results are in accordance with the lowest capacity of DCs to drive immune response of CD8+ T lymphocytes in vivo, impacting in lower steatosis in non-alcoholic steatohepatitis NASH model.

In conclusion, all abovementioned results indicate that loss of MR in myeloid cells impacts in the adaptive CD8+ immune response. However, further analysis about how MR modulates antigen presenting cells to impair CD8+ T lymphocytes function is needed.

• Nombre: Natalia Muñoz Durango
• Laboratorio: IMII
• Mención: Genética Molecular y Microbiología
• Director Tesis: Alexis Kalergis