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

  • Systemic Lupus Erythematosus (G Tsokos, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

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.

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Funding

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.

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  1. Department of Internal Medicine, Rheumatic Diseases Division and Department of Immunology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8884, USA

    Anne B. Satterthwaite

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Satterthwaite, A.B. TLR7 Signaling in Lupus B Cells: New Insights into Synergizing Factors and Downstream Signals. Curr Rheumatol Rep 23, 80 (2021). https://doi.org/10.1007/s11926-021-01047-1

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