ESTROGEN RECEPTOR SIGNALING PROMOTES MONOCYTE ACTIVATION AND DIFFERENTIATION UPON INFLAMMATION IN VIVO (98.20)

17-β-estradiol at physiological levels regulates GM-CSF-mediated dendritic cell (DC) differentiation in vitro by promoting the generation of CD11bintLy6C- DC from myeloid progenitors. In this model, estrogen receptor alpha (ER) signaling induces and sustains elevated levels of interferon regulatory factor 4 (IRF4), a transcription factor critical in this pathway. Such events may relate to the de novo DC differentiation that occurs in vivo upon inflammation during infection or autoimmunity, resulting in inflammatory DC that determine the induction of specific Th cell populations. The current work evaluates whether ER signaling regulates new DC differentiation from blood monocytes during inflammation in vivo, and if this is associated with elevated IRF4 expression. ERα+/+ or ERα-/- mice were immunized subcutaneously with complete Freund’s adjuvant. By day 2 post immunization, compared to ERα-/- mice, ERα+/+ mice harbored an increased frequency of CD115+CD11b+ blood monocytes expressing higher levels of IRF4 and MHC class II. On days 2 and 7, relative to ERα-/- mice, lymph nodes of ERα+/+ mice contained greater numbers of monocyte-derived Gr1+CD11b+ CD11clo inflammatory DC. These data show that during inflammation in vivo, ER signaling promotes monocyte activation, IRF4 expression and differentiation, which leads to increased numbers of a de novo inflammatory DC population in draining lymph nodes.