Chemokines in autoimmune lacrimal gland disease in MRL/MpJ mice.

PURPOSE: MRL/MpJ-fas+/fas+ (MRL/+) and MRL/MpJ-fas(lpr)/fas(lpr) (MRL/lpr) mice undergo spontaneous development of inflammation of the lacrimal and salivary glands, similar to that in the human disorder Sjögren's syndrome. Previous work has shown that these lesions appear to be largely T helper (Th)-2-driven, as evidenced by the substantially greater expression of IL-4 than interferon-gamma. The relative contributions of selected chemokines associated with Th1 and Th2 immune responses were assessed. METHODS: Lacrimal glands from MRL/+ and MRL/lpr mice, at ages 1.5 through 9 months were evaluated by immunohistochemistry for the chemokines monocyte chemoattractant protein (MCP)-1 (also known as chemokine ligand [CCL]-2), MCP-5 (CCL12), thymus activation regulated chemokine (TARC; or CCL17), and macrophage-derived chemokine (MDC; or CCL22). Additional lacrimal glands were tested by real-time RT-PCR for chemokines MCP-1 and -5, which are associated with Th2 and Th1 responses, respectively. RESULTS: By immunohistochemistry a significantly greater proportion of mononuclear inflammatory cells in the lacrimal gland lesions stained for MCP-1 (29%-48% depending on age) compared with MCP-5 (1%-3% 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 studies showed higher transcript levels of MCP-1 compared with MCP-5, in both MRL/+ (median difference, 37.3; P < 0.0001) and MRL/lpr (median difference, 77.1; P < 0.0001) mice. Relative transcripts of MCP-1 increased with age in both MRL/+ mice (P = 0.02) and MRL/lpr mice (P = 0.03). Staining for TARC was present on lacrimal gland ductular cells but not on the infiltrating lymphocytes, and staining for MDC was present on scattered individual cells throughout the lacrimal gland, but not on infiltrating lymphocytes. CONCLUSIONS: The predominant expression of a Th2-associated chemokine in the lacrimal gland lesions in this murine model of Sjögren's syndrome may contribute to the predominantly Th2-type lymphoid infiltrate in these tissues.

Duke Scholars

Author Esen Karamursel Akpek Ophthalmology, Vitreoretinal Diseases & Surgery