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