Estrogen receptor α modulates T cell-mediated alloimmune responses in murine cardiac transplantation [ATAC-seq]

Here, we investigate how estrogen receptor α (ERα) signaling modulates T cell alloimmune responses. We show that T cell-specific ERα knockout (T-ERα KO) prolongs the survival of heart allografts in mice.

This is accompanied by dampened T cell responses characterized by diminished effector function and cytokine production. Furthermore, pharmacological ERα degradation with fulvestrant also prolongs graft survival. Reduced chromatin accessibility at immune-related genes and transcription factor binding sites, together with transcriptomic changes in ERα-deficient T cells indicate that both epigenetic and genetic factors are involved in ERα-mediated modulation of T cell function.