Control of myeloid activity during retinal inflammation

Abstract: Combating myeloid cell-mediated de-struction of the retina during inflammation or neu-rodegeneration is dependent on the integrity of homeostatic mechanisms within the tissue that may suppress T cell activation and their subsequent cy-tokine responses, modulate infiltrating macro-phage activation, and facilitate healthy tissue re-pair. Success is dependent on response of the res-ident myeloid-cell populations [microglia (MG)] to activation signals, commonly cytokines, and the control of infiltrating macrophage activation dur-ing inflammation, both of which appear highly pro-grammed in normal and inflamed retina. The evi-dence that tissue CD200 constitutively provides down-regulatory signals to myeloid-derived cells via cognate CD200–CD200 receptor (R) interac-tion supports inherent tissue control of myeloid cell activation. In the retina, there is extensive neuronal and endothelial expression of CD200. Retinal MG in CD200 knockout mice display nor-mal morphology but unlike the wild-type mice, are present in increased numbers and express nitric oxide synthase 2, a macrophage activation marker, inferring that loss of CD200 or absent CD200R ligation results in “classical ” activation of myeloid cells. Thus, when mice lack CD200, they show increased susceptibility to and accelerated onset o