What is it about?
Nuclear factor-kappa B (NF-κB) signalling mechanisms provide central controls in Sjögren's syndrome (SS), but how these pathways intersect the pathological features of this disease is unclear. The ubiquitin-editing enzyme A20 (tumour necrosis factor-α-induced protein 3, TNFAIP3) serves as a critical inhibitor on NF-κB signalling. In humans, polymorphisms in the A20 gene or a deregulated expression of A20 are often associated with several inflammatory disorders, including SS. Because A20 controls the ectodysplasin-A1 (EDA-A1)/ectodysplasin receptor (EDAR) signalling negatively, and the deletion of A20 results in excessive EDA1-induced NF-κB signalling, this work investigates the expression levels of EDA-A1 and EDAR in SS human salivary glands epithelial cells (SGEC) and evaluates the hypothesis that SS SGEC-specific deregulation of A20 results in excessive EDA1-induced NF-κB signalling in SS.
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Why is it important?
this work is important to evaluate the mechanism responsible of the destruction or replacement of glandular tissue by inflammatory cells and to explain the chronic inflammatory condition and the severe impairment in salivary secretion characterizing Sjögren's syndrome disease
Perspectives
The causes of hypofunction in salivary are complex. The future challenge is to distinguish nonimmunologic mechanisms from immunologic mechanisms in target organs in this unique disease. Identification of gene(s) being responsible for nonimmune pathogenesis using gene targeting models is another way. To create an integrated model that can account for salivary and lacrimal glands hypofunction is ideal. Our current knowledge for gene transcription regulation by the EDA‐A1/EDAR/NF‐κB pathway does not provide a satisfactory mechanistic framework to explain how an incoming activating signal provided by EDA‐A1 would be enabled to activate the transcription of genes involved in the exacerbation of inflammation observed in autoimmune conditions but, conversely, may provide new insights into treating or preventing autoimmunity and inflammation‐based disease.
Margherita Sisto
Universita degli Studi di Bari Aldo Moro
Read the Original
This page is a summary of: Downstream activation of NF-κB in the EDA-A1/EDAR signalling in Sjögren's syndrome and its regulation by the ubiquitin-editing enzyme A20, Clinical & Experimental Immunology, February 2016, Wiley,
DOI: 10.1111/cei.12764.
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