A Critical Role of Th17 Cells in the Development of Murine Sjogeren’s Syndrome

Abstract

Sjögren’s syndrome (SS) is characterized by progressive inflammation and tissue damage of salivary glands (SG) and lacrimal glands, leading to dry-mouth and dry-eye symptoms as a result of reduced saliva and tears secretion. Histopathologically, CD4+ T cells were the major population in the infiltration and mediated tissue destruction. However, a role of IL-17-producing CD4+ T cell (Th17 cell) has not yet been elucidated in SS pathogenesis. In the present study, experimental SS was induced in normal mice by immunization with proteins extracted from SG. A rapid increase of Th17 cells was observed in the spleen and draining cervical lymph node at acute stage. Interestingly, this pattern also emerged in the draining lymph node of non-obese diabetic mice, another murine model of SS. Further, SG-infiltrating Th17 cells were detected and increased along disease progression. In IL-17 deficient (IL-17-/-) mice, no apparent salivary dysfunction and autoantibodies were observed upon immunization. However, upon adoptive transfer of Th17 cells from wild type mice, high titer of autoantibodies, salivary dysfunction with lymphocytic infiltration were fully restored in IL-17-/- mice. Together, our findings have demonstrated a critical role of Th17 cells in SS pathogenesis.