Expressions of lymphotactin and its receptor, XCR, in Lewis rats with experimental autoimmune anterior uveitis.

Background

To demonstrate the expression of lymphotactin and its receptor (XCR) in the iris/ciliary body and popliteal lymph node, and to clarify their roles in experimental autoimmune anterior uveitis (EAAU).

Methods

Uveitis was induced in Lewis rats by injection of melanin-associated antigen into the peritoneum and footpad. At defined time points, mRNA expression levels of lymphotactin and XCR in the iris/ciliary body and popliteal lymph node were measured by semiquantitative polymerase chain reaction. Lymphotactin levels in aqueous humor and serum after immunization were determined by enzyme-linked immunosorbent assay. In a separate experiment, an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC; 200 mg/kg/day), was injected daily into the intraperitoneum after immunization. Cellular sources of lymphotactin were determined by immunhistochemical staining and flow cytometry.

Results

Lymphotactin mRNA was upregulated in the iris/ciliary body with a peak level at day 14, which is in line with the disease course. XCR mRNA was expressed maximally and then declined gradually from days 5 to 21. With an expression pattern similar to that of mRNA expression, lymphotactin in aqueous humor had attracted corresponding numbers of leukocytes. PDTC markedly inhibited the expression of lymphotactin in aqueous humor and serum. Immunohistochemical staining and flow cytometry analysis revealed that the expression of lymphotactin was detected in infiltrated inflammatory cells, dominantly CD8+ T cells, and increased along with inflammation.

Conclusions

The lymphotactin and XCR interaction might direct distinct lymphocytes subsets to inflammatory sites. Lymphotactin could regulate the inflammatory process. Lymphotactin expression may be modulated, at least in part, through the NF-κB signaling pathway.