IL-27 Expression In Salivary Gland Tissues Of Sjögren's Syndrome

Objectives: Recently, the CD4+ TH1/TH2 cell paradigm has undergone a major re-orientation by the discovery of TH17 cells, a new subset of CD4+ T memory cells characterized by their unique ability to secrete IL-17 family cytokines. Recently, we reported that TH17 cells are intimately involved in lymphocytic foci (LF) found in salivary and lacrimal glands of Sjögren's syndrome (SjS) patients as well as animal models of SjS. In our current studies, we have investigated whether the IL-23/TH17 system is up-regulated in SjS because of a defect in the regulatory IL-27 system.

Methods: Sera, saliva and salivary glands of C57BL/6.NOD-Aec1Aec2 mice (a model for primary SjS) were evaluated for both gene and protein expressions of IL-27p28, IL-27EBI3, gp130 and other IL-27-associated molecules using immunohistochemical staining, real-time PCR and Luminex quantification.

Results: Immunohistochemical stainings of submandibular and lacrimal glands from C57BL/6.NOD-Aec1Aec2 mice revealed limited and sparse positive staining for IL-27 throughout the glandular tissue, in contrast to wide-spread strong staining for IL-17 primarily within the LF. Temporal gene expression of IL27p28, and to a lesser degree IL27EBI3, indicated lower levels of IL27 transcripts in submandibular glands of C57BL/6.NOD-Aec1Aec2 mice compared to SjS-non-susceptible C57BL/6 parental mice at the time of SjS disease onset (around 20 wks of age). This was in direct contrast to expression of gp130 (an IL-27 receptor subunit) as well as several molecules (e.g., Stat1 and Stat3) involved in signal transduction pathways and whose expressions were up-regulated.

Conclusions: These results suggest that the IL-23/IL-17/TH17 system is capable of up-regulation in the salivary and lacrimal glands of C57BL/6.NOD-Aec1Aec2 mice at time of disease onset, in part due to a reduced expression of IL-27 known to down-regulate its action. These observations suggest that IL-27 therapy may be an important intervention for SjS patients. (NIH grant R01 DE014344)