Salivary gland tissue expression of interleukin‐23 and interleukin‐17 in Sjögren's syndrome: Findings in humans and mice

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Abstract
Objective Recently, the Th1/Th2 paradigm has been expanded by the discovery of Th17 cells, a subset of CD4+ memory T cells characterized by their unique ability to secrete interleukin‐17 (IL‐17) family cytokines. Importantly, Th17 cells appear to be intimately involved in autoimmunity. We undertook the present study to investigate whether the Th17/IL‐23 system is up‐regulated in Sjögren's syndrome (SS). Methods Sera, saliva, and salivary glands from C57BL/6.NOD‐Aec1Aec2 mice (a model for primary SS), as well as sera, saliva, and salivary gland biopsy specimens obtained from patients with primary SS, were evaluated for IL‐17 and IL‐23 expression by immunohistochemistry, real‐time polymerase chain reaction, and the Luminex system. Results Immunohistochemical stainings of submandibular glands from C57BL/6.NOD‐Aec1Aec2 mice and of salivary gland biopsy specimens from SS patients revealed strong positive staining for both IL‐17 and IL‐23 within lymphocytic foci and diffuse staining on epithelial tissues. Temporal expression of IL‐17 and IL‐23 in submandibular glands of C57BL/6.NOD‐Aec1Aec2 mice correlated with expression of retinoic acid–related orphan receptor γt, the Th17 cell master control gene. While IL‐17 could not be detected in saliva from 4–20‐week‐old C57BL/6.NOD‐Aec1Aec2 mice, this cytokine was present in the blood of mice up to age 16 weeks. This contrasted with sera and saliva from SS patients, in which IL‐17 and IL‐6 were present at varying levels. Conclusion These results suggest that the Th17/IL‐23 system is up‐regulated in C57BL/6.NOD‐Aec1Aec2 mice and SS patients at the time of disease. A correlation between up‐regulated IL‐17/IL‐23 expression and specific clinical manifestations of SS has yet to be identified.