page 2915. The findings suggest that Sjögren's syndrome stems from salivary gland epithelial cells that make interferon (IFN)-γ and then present self-antigens.
During Sjögren's syndrome, the body's immune cells attack moisture-producing cells in salivary glands and tear ducts. The destruction of these cells is initiated by estrogen loss during menopause via the induction of a chromatin-modifying protein called RbAp48, which triggers p53-dependent cell death.
The timing of mouse menopause is difficult to pin down, so to better understand RbAp48's role, the group created mice that overexpress RbAp48 in gland cells. They now find that these mice develop symptoms resembling Sjögren's syndrome.
Epithelial cells from transgenic salivary glands produced IL-18 and IFN-γ, which then induced the expression of MHC class II molecules. These cytokines also stimulated the proliferation of local autoreactive T cells that had previously ignored epithelial self-antigens. IFN-γ and RbAp48 were also found in epithelial cells of patients with Sjögren's syndrome.
Professional APCs seem to be required to start or maintain autoimmunity when estrogen levels are normal, as transferring T cells from transgenic lymph nodes into nontransgenic mice initiated gland cell destruction only if APCs were included. But epithelial cells may be self-sufficient APCs in the absence of estrogen; T cells from the transgenic mice were enough to cause disease in mice whose ovaries had been removed. NL