IADR/AADR/CADR 87th General Session and Exhibition (April 1-4, 2009): Temporal Loss of IL-27-Expression Relative to IL-17 in Sjögren's Syndrome

Objectives: TH17 cells, a newly defined T helper cell population, are a subset of CD4+ T memory cells characterized by their secretion of IL-17 family cytokines. Recently, we reported that TH17 cells are present in lymphocytic infiltrates of salivary glands of both Sjögren's syndrome (SjS) patients and animal models of SjS. Regulation of the TH17 system involves IL-27, a cytokine secreted by dendritic cells. We hypothesized that the TH17 system is up-regulated in SjS because IL-27 gene and protein expressions are defective.

Methods: Salivary glands from male and female C57BL/6.NOD-Aec1Aec2 mice (a model for primary SjS) and C57BL/6 mice (the comparative control) were evaluated for temporal gene and protein expressions of IL-27 versus IL-17 using quantitative real-time PCR and western blotting, respectively. Gene expression levels were quantified against 18S RNA expressions.

Results: Relative gene expressions for both IL-27 and IL-17 in salivary glands of C57BL/6.NOD-Aec1Aec2 mice exhibited similar temporal profiles during development and onset of SjS-like disease. Whereas, IL-17 and IL-27 gene expressions increased through 16 weeks of age before decreasing at time of disease onset, IL-27 protein levels, as determined by Western blots, decreased constantly from 4 weeks of age through time of disease onset, in contrast to levels observed in C57BL/6J control mice. Interestingly, salivary gland tissue from female C57BL/6.NOD-Aec1Aec2 mice showed less IL-27 protein expressions than males.

Conclusions: These results indicate that expression of IL-27 in salivary glands of C57BL/6.NOD-Aec1Aec2 mice decreases during development and onset of SjS-like disease, thus demonstrating no direct correlation with IL-27 transcript levels. As a consequence, we suspect that, with time, TH17 cells are activated due to the lower levels of IL-27, thereby leading to onset of disease. These observations suggest that IL-27 may be an important target for therapeutic intervention.

NIH grants DE014344 & T32AI00760