TY - JOUR
T1 - TLR7 Signaling in Lupus B Cells
T2 - New Insights into Synergizing Factors and Downstream Signals
AU - Satterthwaite, Anne B.
N1 - Funding Information:
A.S. is supported by NIH grants AI122720, AI161307, and AR072598. She is a Southwestern Medical Foundation Scholar in Biomedical Research and holds the Peggy Chavellier Professorship in Arthritis Research and Treatment.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - B cells
KW - Cytokines
KW - Lupus
KW - Signaling
KW - TLR7
KW - Transcription factors
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U2 - 10.1007/s11926-021-01047-1
DO - 10.1007/s11926-021-01047-1
M3 - Review article
C2 - 34817709
AN - SCOPUS:85119886943
SN - 1523-3774
VL - 23
JO - Current Rheumatology Reports
JF - Current Rheumatology Reports
IS - 11
M1 - 80
ER -