Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases

Area of Science:

• Immunology
• Molecular Biology
• Autoimmunity

Background:

• Toll-like receptor 7 (TLR7) typically recognizes microbial RNA but can also target self-RNA, potentially causing autoimmune conditions.
• TLR7 is conventionally believed to reside within endolysosomes to prevent self-reactivity.
• Aberrant TLR7 activation is implicated in the pathogenesis of various autoimmune diseases.

Purpose of the Study:

• To investigate the cellular localization of Toll-like receptor 7 (TLR7).
• To evaluate the therapeutic potential of targeting cell surface TLR7 in autoimmune diseases.

Main Methods:

• Immunofluorescence microscopy to determine TLR7 localization.
• In vitro assays using dendritic cells, macrophages, and B cells to assess TLR7 inhibition by an anti-TLR7 antibody.
• In vivo studies in Unc93b1(D34A/D34A) mice to evaluate the antibody's efficacy in ameliorating TLR7-mediated inflammation.

Main Results:

• Contrary to established views, TLR7 was found on the cell surface of immune cells.
• An anti-TLR7 antibody effectively inhibited TLR7 responses in multiple immune cell types.
• The anti-TLR7 antibody reduced in vivo cytokine production and ameliorated lethal inflammation and progressive autoimmune symptoms in mice.

Conclusions:

• Cell surface TLR7 is a key driver of autoimmune inflammation.
• Targeting cell surface TLR7 with antibodies presents a promising therapeutic strategy for autoimmune diseases.