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

• Published in: Current rheumatology reports Vol. 23; no. 11; p. 80
• Main Author: Satterthwaite, Anne B.
• Format: Journal Article
• Language: English
• Published: New York Springer US 24.11.2021
• Subjects: Animals; Autoimmunity; B-Lymphocytes - metabolism; Humans; Interferon Regulatory Factors; Lupus Erythematosus, Systemic; Medicine; Medicine & Public Health; Mice; Rheumatology; Section Editor; Signal Transduction; Systemic Lupus Erythematosus (G Tsokos; Toll-Like Receptor 7 - metabolism; Topical Collection on Systemic Lupus Erythematosus; Lupus; Signaling; Transcription factors; TLR7; B cells; Cytokines
• ISSN: 1523-3774; 1534-6307
• DOI: 10.1007/s11926-021-01047-1

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, IFNγ, 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 αvβ3 integrin is critical for preventing autoimmunity. Summary 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.