Role of Cholesterol Homeostasis in Lupus Pathogenesis
Abstract
Improper regulation of a specific immune cell called a B cell has been long linked to the development of SLE. A subtype of B cells, termed Autoimmune/Age-associated B cells (ABC), has recently been shown to play a major role in SLE because of their ability to be major producers of the proteins, also known as autoantibodies, that can cause damage in lupus. Expansion of ABCs in SLE is greater in African American patients and correlates with disease activity and clinical manifestations. The environmental triggers that promote the accumulation of ABCs in lupus patients are largely unknown. Our laboratory has found that the expansion of ABCs in mice is controlled by a small family of two molecules. We have found that deleting both of these molecules in mice (leading to a Double Knock-out=DKO) leads to the spontaneous development of lupus in mice that shares many features with the human disease including the fact that the disease primarily affects female mice. We have recently found that manipulating cholesterol levels in these mice can promote the expansion of ABCs and affect the extent of inflammation in different organs in these mice. In this proposal we will investigate the hypothesis that alterations in cholesterol,as could be driven by a Western-diet rich in cholesterol, can affect the accumulation of ABCs and the ability of inflammatory cells to target specific organs and thus contribute to the heterogeneity of SLE.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1192039
Entities
People
- Alessandra Pernis
Organizations
- Hospital for Special Surgery