The role of type I interferon signaling in early dacryoadenitis in the nonobese diabetic mouse model of Sjögren’s disease

Sjogren’s disease (SjD) is a chronic autoimmune disease of the lacrimal and salivary glands. Male nonobese diabetic (NOD) mice spontaneously develop lacrimal gland inflammation by 5-6 weeks of age. As disease progresses, B cells accumulate in the glands and produce antibodies resulting in glandular damage. Disruption of the type I interferon (IFN) signaling pathway protects NOD mice from developing lacrimal gland disease. While we previously showed that there is a lymphocyte-intrinsic role for type I IFN signaling in SjD, the impact of type I IFN signaling on B cell pathogenesis has not been defined. We identified B cell genes and pathways that are upregulated in early lacrimal autoimmunity. Adoptive transfer studies demonstrated that IFNAR1 expression on B cells exacerbates disease. Adoptive co-transfer studies of WT and IFNAR1-deficient cells revealed that intrinsic type I IFN signaling shapes B cell populations in the lacrimal glands and is required for the trafficking of autoreactive B cells to the glands. In vitro studies found that B cell phenotype can be shaped by IFN-α in a dose dependent manner. Together these data demonstrate that type I IFN signaling drives the development of lacrimal gland autoimmunity in NOD mice by shaping B cell phenotype and function.