LAUSR

The human ocular surface epithelium expresses TLR3, which recognizes double-stranded (ds) RNA mimicking polyinosine-polycytidylic acid (polyI:C). Its stimulation induces the secretion of the inflammatory cytokines such as interleukin (IL)-6, IL-8, and type I interferon. The cytoplasmic helicase proteins RIG-I and MDA5 are also expressed on the ocular surface. We investigated the function of TLR3 in the cornea of CD11c- YFP+ and TLR3 KO CD11c- YFP+ mice. We also examined the function of IPS-1, an adaptor molecule common to RIG-I and/or MDA5, in IPS-1 KO CD11c- YFP+ mice. In the central corneal epithelium of CD11c- YFP+ mice, the infiltration of CD11c- YFP+ cells was significantly upregulated 48 h after polyI:C stimulation; it was significantly downregulated in the stromal layer of their central and peripheral cornea. On the other hand, in the corneal epithelium of TLR3 KO CD11c- YFP+- and wild-type mice, the movement of CD11c- YFP+ cells was different from CD11c- YFP+ mice. This suggests that TLR3 knock-out (KO) interferes with their movement from the peripheral- to the central cornea or lymph nodes and that it may be similar in IPS-1 KO CD11c-YFP+ - and wild-type mice. Under normal conditions, the number of CD11c- YFP+ cells in the central and peripheral corneal epithelium, but not in the stromal layer, is significantly greater in TLR3 KO CD11c- YFP+- than CD11c- YFP+ mice. In IPS-1 KO CD11c- YFP+ mice, their number in the stromal layer, but not in the epithelium of the central and peripheral cornea, was significantly greater than in CD11c- YFP+ mice. Our findings suggest that CD11c+ dendritic cell (DC) migration in the corneal epithelium is regulated by TLR3, whereas CD11c+ DC migration in the stromal layer of the cornea is regulated by IPS-1. These observations, together with our earlier findings, imply that TLR3 and IPS-1 contribute distinctly to the regulation of innate immune responses and tissue inflammation elicited by CD11c+ DCs to maintain homeostasis in corneal tissues.