Objective. Sjo ¨gren's syndrome (SS) is a chronic autoimmune disease of unknown etiology that targets salivary and lacrimal glands and may be accompanied by multiorgan systemic manifestations. To further the understanding of immunopathology associated with SS and identify potential therapeutic targets, we undertook the present study comparing the gene expression profiles of salivary glands with severe inflammation versus those of salivary glands with mild or no disease.
Methods. Using microarray profiling of salivary gland tissue from patients with SS and control subjects, we identified target genes, which were further characterized in tissue, serum, and cultured cell populations by real-time polymerase chain reaction and protein analysis.
Results. Among the most highly expressed SS genes were those associated with myeloid cells, including members of the mammalian chitinase family, which had not previously been shown to be associated with exocrinopathies. Both chitinase 3-like protein 1 and chitinase 1, highly conserved chitinase-like glycoproteins (one with enzymatic activity and one lacking enzymatic activity), were evident at the transcriptome level and were detected within inflamed tissue. Chitinases were expressed during monocyte-to-macrophage differentiation and their levels augmented by stimulation with cytokines, including interferon-␣ (IFN␣).
Conclusion. Because elevated expression of these and other macrophage-derived molecules corresponded with more severe SS, the present observations suggest that macrophages have potential immunopathologic involvement in SS and that the tissue macrophage transcription profile reflects multiple genes induced by IFN␣.
Sjo ¨gren's syndrome (SS) is a chronic autoimmune disease that affects salivary and lacrimal exocrine glands with variable severity and may be accompanied by multiorgan systemic manifestations. In primary SS, environmental triggers are thought to target individuals with a genetic predisposition. SS may also occur in association with other autoimmune diseases. Although exocrine gland dysfunction in SS was initially considered to be the consequence of an aberrant CD4ϩ T lymphocyte Th1 cell response, new evidence suggests that a contribution of lymphocytes of Th17 cell lineage may also be fundamental to exocrine gland dysfunction (1-5). Elevated levels of Th17 cell-generated cytokines, including interleukin-17 (IL-17), as well as IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF), proinflammatory mediators associated with host response to infections, also influence recruitment and activation of innate cells (6). Among the recruited populations are myeloid cells, particularly macrophages,