Abstract
Abstract Sjogren’s disease is a chronic autoimmune disease of the lacrimal and salivary glands characterized by foci of inflammation in the tissue composed of aggregations of lymphocytes. Male non-obese diabetic (NOD) mice spontaneously develop autoimmunity of the lacrimal glands. Tregs from these mice are dysfunctional. Disruption of the type I interferon (IFN) signaling pathway protects NOD mice from developing lacrimal gland disease. Whether type l IFN signaling drives lacrimal gland protective Treg dysfunction is not known. Here we investigated the role of type l IFN in modulating Treg phenotype and function. Through adoptive transfer studies comparing cells from wild-type or IFNAR1-deficient donor mice, we found that recipients of IFNAR1-deficient cells had fewer foci of inflammation. IFNAR1 expression was correlated with a population of CD44loCD62Lhi Tregs. Co-adoptive transfer of both WT and IFNAR1-deficient cells determined that this altered Treg phenotype was due to intrinsic type l IFN signaling. In vitro studies suggest that Treg phenotype can be shaped by IFNα in a dose dependent manner. Ongoing in vivo studies will interrogate the impact of IFNAR1 expression on Treg function. Type l IFN signaling plays a role in shaping Treg phenotype and may antagonize Treg function. These studies will help define the role of type l IFN signaling in early pathogenesis of Sjögren’s disease and may provide insight into other systemic autoimmune diseases. Supported by grants from NIH (R01EY027731-01A1)
Published Version
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