DNA graphic

Stefania Gallucci, MD

Associate Professor

Temple University

Microbiology, Immunology and Inflammation


Sex hormones, dendritic cells, and the IFN signature in lupus

Dendritic cells (DCs) are pivotal immune regulators and require type I Interferons (I-IFNs) to activate. Both DCs and I-IFNs are important in Systemic Lupus Erythematosus (SLE). DCs from lupus-prone mice constitutively overexpress I-IFN responsive genes resembling the IFN Signature found in SLE patients. Since this signature is present in pre-diseased mice, it may contribute to disease pathogenesis. We hypothesize that estrogens are required for the expression of the IFN signature by DCs from lupus-prone mice and aim to study the effects of estrogen on the I-IFN response in DC subsets from female and male lupus-prone mice, constitutively and upon I-IFN stimulators in vitro and in vivo. To understand the molecular mechanisms of estrogen regulation of I-IFNs, we will study expression and functions of the estrogen receptors, TLRs and pivotal transcription factors and signaling molecules downstream of I-IFN receptors. Finally, we hypothesize that in vivo DCs contribute to lupus pathogenesis primarily if they can respond to estrogens and by producing I-IFN. To this end, we will investigate disease outcome in lupus mouse models in which disease will be modulated by an I-IFN-producing adenovirus, by injection of DCs that lack ERalpha (NZBxNZW F 1) and by Fulvestrant, an estrogen selective receptor inhibitor.

Together, ManyOne Can make a difference!
Stay informed about events, research developments, and ways you can help. Sign up for updates