Announcement of Oral Dissertation Defense for Holly Ryan


Holly Ryan

PI: Dr. Erika Moore

Role of Monocytes in Promoting SLE-Associated Endothelial Cell Dysfunction in a Hydrogel Model of the Microvasculature

Date: 8/14/2023

Time: 9:00AM

Location: C1-003/ Zoom Link:


Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that causes significant morbidity and mortality, especially in women of child-
bearing age. In SLE, antibodies are produced against self-antigens such as DNA or other nuclear components. Recognition of these self-antigens
may occur almost anywhere in the body, leading to an immune reaction against otherwise healthy tissue. The pathogenesis of SLE is not well
understood but is believed to be a combination of various genetic and environmental factors. For example, certain ancestral groups are at much
higher risk of developing SLE than others; environmental cues such as infection with certain viruses are also known to play a role in disease
development. In addition, although plasma cells are the immune cell type directly responsible for producing antibodies, the pathogenesis of SLE is
believed to involve many different cell types of both the adaptive and innate systems.
In this work, we study the activity of monocytes, which are phagocytic cells of the innate immune system, to investigate their role in the
inflammatory processes involved in SLE. Toll-like receptor (TLR) 7 is known to play a role in SLE pathogenesis, and so we use R848, an agonist to this
receptor, to identify how certain inflammatory pathways in SLE may be affected by TLR7 overactivity. We quantify the upregulation of the
transcription and translation of inflammatory cytokines in monocytes from SLE patients and compare results to the upregulation seen when TLR7 is
exogenously stimulated via R848 administration. Finally, we use a three-dimensional hydrogel culturing system to investigate interactions between
monocytes and endothelial cells based on the activation or disease state of the monocytes. This assay may provide insight into how monocytes
promote microvascular inflammation in the setting of SLE.