Chemokine Expression in Autoimmune Lacrimal Gland Disease in MRL/MpJ Mice

Abstract

Abstract: : Purpose: MRL/MpJ-fas⁺/fas⁺(MRL/+) and MRL/MpJ-fas^lpr/fas^lpr (MRL/lpr) mice are congeneic substrains that spontaneously develop destructive inflammation of the lacrimal and salivary glands, representing a model for human Sjögren’s syndrome. Previous work on cytokine expression profiles suggested that these lacrimal gland lesions appear to be largely T helper (Th) 2-driven. In this study, the relative contributions of chemokines MCP-1 and MCP-5, implicating Th2 and Th1 immune responses respectively, were assessed. Methods: Lacrimal glands were harvested from MRL/+ and MRL/lpr mice, at ages 6 weeks through 9 months. ABC staining on frozen sections and real time RT-PCR on the extracted RNA were performed to quantify the chemokine expression profiles. Age-matched BALB/c mice were used as controls. Results: Immunohistochemical studies demonstrated a significantly greater proportion of cells in the lacrimal gland lesions staining for MCP-1 (29 to 48% of total inflammatory cells depending on age) as compared to MCP-5 (1 to 3% of total inflammatory cells depending on age) both in MRL/+ (mean difference 34.2%, p<0.001) and MRL/lpr (mean difference 33.6%, p<0.001) substrains. Real time RT-PCR analyses showed a 2- to 110-fold higher transcript levels of MCP-1 as compared to MCP-5, in both MRL/+ (2.6 to 66.9 depending on age) and MRL/lpr (23.6 to 110.4 depending on age) mice, confirming the immunohistochemistry results. The ratio of MCP-1 to MCP-5 mRNA transcripts increased with increasing age and extent of disease in both substrains. Conclusions: The chemokine expression profile is consistent with the concept that the lacrimal gland lesions in MRL/MpJ mice are largely Th2-mediated.

Keywords: lacrimal gland • inflammation • pathology: experimental