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 s...

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Bibliographic Details
Published in:Current rheumatology reports 2021-11, Vol.23 (11), p.80-80, Article 80
Main Author: Satterthwaite, Anne B.
Format: Article
Language:English
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
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Summary: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.
ISSN:1523-3774
1534-6307
DOI:10.1007/s11926-021-01047-1