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Chemokine and chemokine receptor expression during experimental autoimmune uveoretinitis in mice
Hiroshi Keino1, Masaru Takeuchi, Takeshi Kezuka
1Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114, USA. keino@vision.eri.harvard.edu
Background:
Chemokines act as chemoattractants and activators of specific leukocytes at the site of inflammation. In this study, we investigated serial expression of chemokines and chemokine receptors in the eye with experimental autoimmune uveoretinitis (EAU) using RNAse protection assay, and confirmed their expression by immunohistochemical staining.
Methods:
B10.A mice were immunized with 50 micro g of interphotoreceptor retinoid binding protein (IRBP) emulsified in complete Freund's adjuvant in order to induce EAU. The eyes were enucleated 0, 7, 14 and 21 days after IRBP immunization to analyze mRNA expression of chemokines and chemokine receptors in the posterior segment. In addition, expression of IP-10 and CXCR3 was analyzed by immunohistochemistry.
Results:
The gene expression of RANTES, IP-10, and MCP-1 was upregulated on day 14 after immunization (early stage of EAU). The expression of chemokine receptors (CCR2 and CCR5) associated with Th1-type T cells correlated with their appropriate ligands. Furthermore, immunohistochemical study showed that IP-10 and CXCR3, the receptor for IP-10, were strongly expressed in the posterior segment of the eyes from mice with EAU.
Conclusion:
These results suggest that RANTES, IP-10 and MCP-1 may contribute to the recruitment of Th1-type T cells into the eye during the development of EAU in mice.