Leading the way to a cure


Activation and Inhibition of TLR Activity in Autoreactive B Cells

Marshak-Rothstein, Ann, PhD

Boston University School of Medicine

Systemic lupus is characterized by the excessive production of a wide range of autoantibodies such as chromatin and ribonucleoproteins specific for self antigens that contain DNA or RNA. These antibodies and/or immune complexes deposit in blood vessel walls, kidney cells and joints, contributing to complications endemic to lupus. Studies from Dr. Marshak-Rothstein’s laboratory and others’ find that these complexes are particularly effective at switching on the immune system, often working through a family of receptors called toll-like receptors or TLRs. 

One receptor, TLR7, recognizes mammalian RNAs. Exactly which mammalian RNAs this receptor recognizes, and how this recognition triggers autoimmune disease, remains a key question. Thus, one goal of this project is to better define the properties of mammalian RNA that lead to TLR reactivity and identify the pathological and environmental conditions that might favor the release of these forms of RNA. 

Another goal is to determine how TLR activation of scavenger cells (cells that clean up dead cells) regulates the response to and removal of cell debris. 

The final goal is to extend the analysis of potential TLR7 inhibitors to other types of small molecules. 

What does this study mean for people with lupus? Identifying ways to inhibit TLR7 and TLR9 may provide important therapeutic strategies for people with lupus and other systemic autoimmune diseases.

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