Estrogen receptor modulates microglia-mediated inflammation

Microglial cell ramified in culture expressing surface OX-42 (red) and CD86 (green).

Image credits Wilma Friedman Lab

Females have an increased susceptibility to develop autoimmune diseases. Female patients who develop multiple sclerosis for example largely outnumber male patients in a ratio of 3 to 1. This study, presented in a recent issue of Cell by Saijo and colleagues, explores a molecular mechanism that could possibly explain why gender is such an important factor in the development of MS.  Saijo and colleagues also explore in a series of elegant experiments how microglia regulate inflammation in response to various stimuli in the CNS.   

Abstract of the study:

Microglia and astrocytes play essential roles in the maintenance of homeostasis within the central nervous system, but mechanisms that control the magnitude and duration of responses to infection and injury remain poorly understood. Here, we provide evidence that 5-androsten-3b,17b-diol (ADIOL) functions as a selective modulator of estrogen receptor (ER)b to suppress inflammatory responses of microglia and astrocytes. ADIOL and a subset of synthetic ERb-specific ligands, but not 17b-estradiol, mediate recruitment of CtBP corepressor complexes to AP- 1-dependent promoters, thereby repressing genes that amplify inflammatory responses and activate Th17 T cells. Reduction of ADIOL or ERb expression results in exaggerated inflammatory responses to TLR4 agonists. Conversely, the administration of ADIOL or synthetic ERb-specific ligands that promote CtBP recruitment prevents experimental autoimmune encephalomyelitis in an ERb-dependent manner. These findings provide evidence for an ADIOL/ERb/ CtBP-transrepression pathway that regulates inflammatory responses in microglia and can be targeted by selective ERb modulators

Full paper here