Estradiol regulates the expression of CD45 splicing isoforms in lymphocytes

CD45, a common leukocyte antigen expressed on the surface of all nucleated hematopoietic cells, indicates the developmental stage and functional status of lymphocytes by its alternative splicing isoforms. Estrogen is correlated with the immune activity of lymphocytes and is involved in the sex bias of several human autoimmune diseases, but the effect of estrogen on the expression of the CD45 splicing isoforms remains unknown. In the present study, a potential estrogen response element was identified on the opposite strand of the CD45 gene by bioinformatics software prediction. The results from RT-qPCR results showed that the expression levels of CD45RO isoform and CD45 antisense RNA were increased after the lymphocytes were treated with 10 nM 17beta-estradiol, and this effect of 17beta-estradiol was reversed when the lymphocytes were cotreated with an estrogen receptor antagonist. Moreover, bisulfite sequencing PCR showed that CD45 DNA methylation in lymphocytes was increased after the treatment with 10 nM 17beta-estradiol. In conclusion, estradiol regulated the expression of CD45 in an estrogen receptor-dependent manner and was associated with CD45 antisense RNA and DNA methylation. The results helped elucidate the regulatory mechanism of the expression of CD45 isoforms and the correlation between estrogen levels and immune activity in females.