Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B Cell Autoreactivity
Annual rept. 1 Jul 2008-30 Jun 2009
FEINSTEIN INST FOR MEDICAL RESEARCH MANHASSET NY
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Systemic lupus erythematosus SLE is an autoimmune disease that occurs preferentially in women. In murine models of SLE, it is clear that increased or sustained high physiologic levels of estradiol can accelerate onset of disease and exacerbate disease severity. We have shown that estradiol alters B cell maturation in vivo but does so in a genetically restricted fashion. We have also shown that estradiol can act directly on B cells to alter B cell receptor BCR signalling strength. This proposal is to understand which estrogen receptors mediate the effects of estradiol on B cell survival, maturation and activation in order to assess whether hormonal manipulation has a potential therapeutic role in SLE. The proposal is further designed to ask why estradiol affects B cell function in mice of one genetic background but not another.
- Medicine and Medical Research