Abstract
BackgroundSjögren’s syndrome (SjS), one of the most common autoimmune diseases, impacts millions of people annually. SjS results from autoimmune attack on exocrine (salivary and lacrimal) glands, and women are nine times more likely to be affected than men. To date, no vaccine or therapeutic exists to treat SjS, and patients must rely on lifelong therapies to alleviate symptoms.MethodsOral treatment with the adhesin from enterotoxigenic Escherichia coli colonization factor antigen I (CFA/I) fimbriae protects against several autoimmune diseases in an antigen (Ag)-independent manner. Lactococcus lactis, which was recently adapted to express CFA/I fimbriae (LL-CFA/I), effectively suppresses inflammation by the induction of infectious tolerance via Ag-specific regulatory T cells (Tregs), that produce IL-10 and TGF-β. To test the hypothesis that CFA/I fimbriae can offset the development of inflammatory T cells via Treg induction, oral treatments with LL-CFA/I were performed on the spontaneous, genetically defined model for SjS, C57BL/6.NOD-Aec1Aec2 mice to maintain salivary flow.ResultsSix-week (wk)-old C57BL/6.NOD-Aec1Aec2 mice were orally dosed with LL-CFA/I and treated every 3 wks; control groups were given L. lactis vector or PBS. LL-CFA/I-treated mice retained salivary flow up to 28 wks of age and showed significantly reduced incidence of inflammatory infiltration into the submandibular and lacrimal glands relative to PBS-treated mice. A significant increase in Foxp3+ and IL-10- and TGF-β-producing Tregs was observed. Moreover, LL-CFA/I significantly reduced the expression of proinflammatory cytokines, IL-6, IL-17, GM-CSF, and IFN-γ. Adoptive transfer of CD4+ T cells from LL-CFA/I-treated, not LL vector-treated mice, restored salivary flow in diseased SjS mice.ConclusionThese data demonstrate that oral LL-CFA/I reduce or halts SjS progression, and these studies will provide the basis for future testing in SjS patients.
Highlights
Sjögren’s syndrome (SjS), one of the most common autoimmune diseases, impacts millions of people annually
Evaluation of SjS mice regulatory T cell (Treg) expression levels CD4+ T cell analysis was performed on diseased SjS mice to discern if these showed a depression in Regulatory T cells (Tregs) levels
Isolated lymphocytes from head and neck lymph nodes (HNLNs) and spleens were stained for expression of IL-10, CD25, and Foxp3
Summary
Sjögren’s syndrome (SjS), one of the most common autoimmune diseases, impacts millions of people annually. SjS results from autoimmune attack on exocrine (salivary and lacrimal) glands, and women are nine times more likely to be affected than men. Sjögren’s syndrome (SjS) is an autoimmune chronic inflammatory disease affecting primarily the lacrimal and salivary glands. SjS is a debilitating disease affecting 3.1 million individuals in the USA [2], with woman being nine times more likely to be afflicted than men [2, 3]. SjS is characterized by lymphocyte infiltrates in the glands. Both T cells and accompanied activated B cells have pathogenic roles in primary Sjögren’s syndrome immunopathology [5, 6]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call