Investigating the role of interferon-alpha in Sjögren’s Disease (101.36)

Abstract

Abstract We have previously demonstrated that IL14a transgenic mice (IL14aTG) reproduce features of Sjögren’s disease (SD) seen in patients in the same relative time frame, including autoantibodies, early destruction of the salivary and lachrymal glands, infiltration of the salivary and lachrymal glands with lymphocytes, lymphocytic pneumonia, mild renal disease and eventually lymphoma (J.Immunol. 177: 5676, 2006 and Clin. Immunol. 130:304, 2009). We have more recently demonstrated that lymphotoxin is an important early mediator of salivary gland injury in IL14aTG mice and patients with SD (J.Immunol. 185: 6355, 2010). In our current studies we investigate the role of interferon-alpha (IFN-α) in SD in IL14aTG mice. We demonstrate that IL14aTG mice lacking the type I IFN receptor (IL14aTG.IFNa/bR-/-) have the same early injury to the submandibular glands as IL14aTG mice. However, IL14aTG.IFNa/bR-/- do not get the later parotid gland injury that is seen in IL14aTG mice. Both IL14aTG mice and IL14aTG.IFNa/bR-/- get lung injury, but IL14aTG mice get a lymphocytic pneumonia and IL14aTG.IFNa/bR-/- get a mild perivascular and peribronchial lymphocytic infiltration. Thus, IFN-α is not critical in early stages of SD but involved in disease manifestations that occur after original salivary gland injury. These data have important implications for the use of IFN-α inhibitors in the treatment of SD.