Anti-TLR7 Antibody Protects Against Lupus Nephritis in NZBWF1 Mice by Targeting B Cells and Patrolling Monocytes

Front Immunol. 2021 Nov 11;12:777197. doi: 10.3389/fimmu.2021.777197. eCollection 2021.


Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and multiple organ damage. Toll-like receptor 7 (TLR7), an innate immune RNA sensor expressed in monocytes/macrophages, dendritic cells (DCs), and B cells, promotes disease progression. However, little is known about the cellular mechanisms through which TLR7 drives lupus nephritis. Here, we show that the anti-mouse TLR7 mAb, but not anti-TLR9 mAb, protected lupus-prone NZBWF1 mice from nephritis. The anti-TLR7 mAb reduced IgG deposition in glomeruli by inhibiting the production of autoantibodies to the RNA-associated antigens. We found a disease-associated increase in Ly6Clow patrolling monocytes that expressed high levels of TLR7 and had upregulated expression of lupus-associated IL-10, CD115, CD31, and TNFSF15 in NZBWF1 mice. Anti-TLR7 mAb abolished this lupus-associated increase in patrolling monocytes in the circulation, spleen, and glomeruli. These results suggested that TLR7 drives autoantibody production and lupus-associated monocytosis in NZBWF1 mice and, that anti-TLR7 mAb is a promising therapeutic tool targeting B cells and monocytes/macrophages.

Keywords: autoantibody; inhibitory monoclonal antibody; lupus nephritis; monocytes; toll-like receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / immunology*
  • Autoantigens / immunology
  • Autoimmunity
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Biomarkers
  • Disease Models, Animal
  • Disease Susceptibility / immunology
  • Gene Expression Regulation
  • Immunoglobulin G / immunology
  • Immunohistochemistry
  • Immunophenotyping
  • Lupus Nephritis / drug therapy
  • Lupus Nephritis / etiology*
  • Lupus Nephritis / metabolism*
  • Lupus Nephritis / pathology
  • Mice
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Toll-Like Receptor 7 / antagonists & inhibitors*
  • Toll-Like Receptor 7 / immunology*


  • Autoantibodies
  • Autoantigens
  • Biomarkers
  • Immunoglobulin G
  • Toll-Like Receptor 7