Loading...
 

Volume 26, Issue 1, April 2015

Sign in to download the Issue in PDF format.

Mediterr J Rheumatol 2015; 26(1): 77-79
Signal transduction via TLR3 increases synthesis and nuclear translocation of autoantigen Ro52/TRIM21 in epithelial cells of salivary glands through the interferon I pathway
Abstract

Objective: Upregulated expression of Ro52/TRIM21, Ro60/TROVE2 and La/SSB autoantigens has been described at the salivary gland epithelial cells (SGEC) of patients with Sjögren's syndrome (SS). SGECs, the key regulators of autoimmune SS responses, express high levels of surface functional TLR3, whereas Ro52/TRIM21 negatively regulates TLR3-mediated inflammation. Herein, we investigated the effect of TLR3-signaling on the expression of Ro52/TRIM21, as well as Ro60/TROVE2 and La/SSB autoantigens, by SGECs.

Methods: The effect of TLR3- or TLR4-stimulation on autoantigen expression was evaluated by polyI:C or LPS treatment, respectively, of SGEC-lines (10 from SS-patients, 12 from non-SS controls) or HeLa cells, followed by analysis of mRNA and protein expression.

Results: PolyI:C, but not LPS, resulted in a two-step induction of Ro52/TRIM21 mRNA expression by SGECs, a 12-fold at 6-hrs followed by a 2.5-fold increment at 24-48-hrs, whereas it induced a late 2-fold upregulation of Ro60/TROVE2 and La/SSB mRNAs at 48-hrs. Although, protein expression levels were not significantly affected, the late upregulation of Ro52/TRIM21 mRNA was accompanied by protein redistribution, from nucleolar-like pattern to multiple coarse dots spanning throughout nucleus. These late phenomena were significantly mediated by IFNβ production, as attested by cognate secretion and specific inhibition experiments and associated with IRF3 degradation. TLR3-signaling had similar effects on SGECs obtained from SS patients and controls, whereas it did not affect the expression of these autoantigens in HeLa cells.

Conclusion: TLR3-signaling regulates the expression of autoantigens by SGECs, implicating innate immunity pathways in their overexpression at inflamed tissues and possibly in their exposure to immune system.