As a specialized organ of the brain, the eye is a classic privileged immune site in which immune responses are suppressed. Because of the BOB, entry of immunologic cells and molecules was considered to be forbidden in the eye. Recently, based on accumulating evidence, it was suggested that immune privilege is an immunological niche in which a specialized, well-orchestrated collaboration between the innate and adaptive arms of the immune system is constructed.
3 RPE cells, beneath the neural retina, are the key cellular component of the BOB. TLRs, complement receptor, CD64, and MHC I and II molecules are expressed on the surface of RPE.
3 Orchestrating innate and adaptive immunity, RPE cells play a crucial role in regulating the immune homeostasis of the eye.
1 TLR pathways comprise the main component of the innate immune system. After binding with their special ligands, TLRs initialize a “toll rush” and generate effectors. Endowed with many TLRs, RPE cells are strategically situated to provide a rapid defense for the retina.
6 The various roles played by the TLR4 pathway in intraocular disease have been well documented. Oxidative stress, mitochondrial DNA damage, chronic inflammation, and angiogenesis (basic pathologic features of AMD) in the retina can be induced by activation of the TLR4 pathway.
7,8 For example, appropriate stimulation by LPS at a low dose can decrease the levels of IL-6 and IL-8 in corneal stroma cells, and prevent excessive inflammatory response to
Aspergillus fumigatus .
24 In the present study, we found that expression of IgG in RPE cells can be elevated by LPS in a concentration- and duration-dependent fashion. Moreover, downregulation of IgG in RPE resulted in a decrease of TLR4, adaptor molecules, the NFκB pathway, and final generation of TNF-α when under stimulation by LPS. TNF-α is a classic effector of the TLR4 pathway, and has been confirmed to protect neurons from damage induced by inflammation at low concentrations.
22,25 The present study showed that upon exposure to graded concentrations of IgG, expression of TLR4 and production of TNF-α by RPE is elevated in a dose-depended manner that plots a reverse U-shaped curve, and the maximal level of TNF-α is under the noninjurious threshold in a slice culture of the brain.
25 These data raise the possibility that IgG may be a terminal effector of the TLR4 pathway, and it in turn has a positive regulatory effect on this pathway and may be protective of RPE under physiologic conditions.