TLR7 Signaling in Lupus B Cells: New Insights into Synergizing Factors and Downstream Signals

Purpose of the Review Systemic lupus erythematosus (SLE) is driven by nucleic acid-containing antigens that stimulate endosomal TLRs. We review new advances in our understanding of how TLR7 signaling in B cells drives autoimmunity. Recent Findings Pathogenic B cell responses to TLR7 engagement are shaped by the disease-associated cytokine environment. TLR7, IFN gamma, and IL-21 together promote the formation of autoreactive germinal centers and the ABC/DN2 B cell subset. BAFF and type 1 IFNs enhance autoantibody production from transitional B cells in concert with TLR7. TLR7 signaling components STAT1, BANK1, IRF5, SLC15A4, and CXorf21/TASL are associated genetically with SLE and important for lupus development in mice, while role of T-bet is controversial. Proper control of TLR7 trafficking by UNC93B1, syntenin-1, and alpha v beta 3 integrin is critical for preventing autoimmunity. A better understanding of TLR7 signaling has revealed potential new therapeutic approaches for SLE, several of which are being tested in animal models or clinical trials.

Automated summary

New research has shown that TLR7 signaling plays a crucial role in driving autoimmune responses in B cells, influenced by the disease-associated cytokine environment. TLR7, IFN gamma, and IL-21 work together to promote the formation of autoreactive germinal centers and the ABC/DN2 B cell subset in systemic lupus erythematosus (SLE).