Title : Pathophysiological role of Id4 for salivary gland homeostasis and IgG4-related diseases
Abstract:
Salivary glands are physiologically orchestrated by the coordinated balance between cell differentiation, proliferation, apoptosis, and interactions between epithelial, mesenchymal, endothelial and neuronal cells. They are also involved in manifestation of Sjögren's syndrome (SS) or IgG4-related disease (IgG4-RD). However, little is known about salivary gland homeostasis and causal relation to these diseases. Inhibitor of DNA binding/differentiation 4 (Id4) is an Id protein involved in the transcriptional control of many biological events, including differentiation. We revealed that Id4-deficient mice showed accelerated differentiation of submandibular glands but with being smaller size compared to those of wild-type littermates. In addition, dry mouth symptoms and Th17 expansion in splenocytes were also observed in the absence of Id4. Furthermore, Id4 levels in the salivary glands of IgG4-RD, but not SS, patients were significantly decreased compared to those of healthy controls. Integrated miRNA-mRNA analysis revealed that miR-486-5p was upregulated in IgG4-RD patients and may regulate Id4 at the lesion sites. Together, these results provide evidence that Id4 regulates salivary gland differentiation and has a critical association between Id4 downregulation and IgG4-RD pathogenesis.
Audience take away:
- Our study indicated that Id4 regulates normal salivary gland differentiation and its decreased expression leads to disruption of salivary gland homeostasis.
- Our findings will help for better understanding about the role of miR-486-5p and Id4 in the pathogenesis of IgG4-RD.
