| First Author | Szczerba BM | Year | 2013 |
| Journal | J Dent Res | Volume | 92 |
| Issue | 5 | Pages | 444-9 |
| PubMed ID | 23533183 | Mgi Jnum | J:279155 |
| Mgi Id | MGI:6359353 | Doi | 10.1177/0022034513483315 |
| Citation | Szczerba BM, et al. (2013) Type I interferon receptor deficiency prevents murine Sjogren's syndrome. J Dent Res 92(5):444-9 |
| abstractText | In Sjogren's Syndrome (SS), inherent glandular defects, autoimmunity, and mononuclear cell infiltration within the salivary glands cause reduced salivation leading to xerostomia. Excessive production of type I interferons (IFN), triggered by environmental and genetic factors, is considered pathogenic in this disorder. However, whether type I IFN production is causative or an outcome of the disease process is not known. To address this question, we introduced a deficiency of interferon alpha receptor 1 (Ifnar1) into B6.Aec1Aec2 mice, which are known to have the genetic loci necessary for developing a SS-like disorder. This new mouse strain, B6.Aec1Aec2Ifnar1 (-/-), lacking type I IFN-mediated signaling, was characterized for pilocarpine-induced salivation, the presence of serum autoantibodies, sialoadenitis, and dacryoadenitis. Compared with the B6.Aec1Aec2Ifnar1 (+/+) (wild-type) mice, the B6.Aec1Aec2Ifnar1 (-/-) (knockout) mice had significantly lower mononuclear cell infiltration in the salivary and lacrimal glands. The knockout mice were completely protected from salivary gland dysfunction. Surprisingly, they had a robust autoantibody response comparable with that of the wild-type mice. These findings demonstrate that, in the absence of type I IFN-mediated signaling, systemic autoantibody responses can be dissociated from glandular pathology. Our study suggests that, in genetically susceptible individuals, the type I IFN pathway can instigate certain features of SS. |
