TLR7 Signaling Drives the Development of Sjögren's Syndrome

Area of Science:

• Immunology
• Autoimmunity
• Rheumatology

Background:

• Sjögren's syndrome (SS) is a chronic autoimmune disease primarily targeting salivary and lacrimal glands.
• SS can coexist with other autoimmune conditions like systemic lupus erythematosus (SLE).

Purpose of the Study:

• To investigate the role of Toll-like receptor 7 (TLR7) signaling in the pathogenesis of Sjögren's syndrome.
• To determine if TLR7 signaling is essential for SS-like pathology observed in TLR8-deficient mice.

Main Methods:

• Utilized TLR8-deficient (TLR8ko) and double TLR7/8-deficient (TLR7/8ko) mouse models.
• Analyzed SS-like phenotypes including sialadenitis, autoantibody production, immune complex deposition, and cytokine profiles.
• Assessed salivary gland histology, ectopic lymphoid structures, and inflammatory marker expression in mouse models and primary SS patient samples.

Main Results:

• TLR8ko mice developed SS-like pathology, including sialadenitis and autoantibody production, driven by increased TLR7 signaling.
• These phenotypes were abrogated in TLR7/8ko mice, confirming TLR7 dependency.
• Elevated TLR7 expression and correlated inflammatory markers (TNF, LT-α, CXCL13, CXCR5) were found in salivary glands of primary SS patients.

Conclusions:

• TLR7 signaling plays a critical role in driving both local and systemic manifestations of Sjögren's syndrome.
• Targeting TLR7 signaling presents a potential therapeutic strategy for SS patients.