Immune Privilege: The Microbiome and Uveitis.

Immune privilege (IP), a term introduced to explain the unpredicted acceptance of allogeneic grafts by the eye and the brain, is considered a unique property of these tissues. However, immune responses are modified by the tissue in which they occur, most of which possess IP to some degree. The eye therefore displays a spectrum of IP because it comprises several tissues. IP as originally conceived can only apply to the retina as it contains few tissue-resident bone-marrow derived myeloid cells and is immunologically shielded by a sophisticated barrier - an inner vascular and an outer epithelial barrier at the retinal pigment epithelium. The vascular barrier comprises the vascular endothelium and the glia limitans. Immune cells do not cross the blood-retinal barrier (BRB) despite two-way transport of interstitial fluid, governed by tissue oncotic pressure. The BRB, and the blood-brain barrier (BBB) mature in the neonatal period under signals from the expanding microbiome and by 18 months are fully established. However, the adult eye is susceptible to intraocular inflammation (uveitis; frequency ~200/100,000 population). Uveitis involving the retinal parenchyma (posterior uveitis, PU) breaches IP, while IP is essentially irrelevant in inflammation involving the ocular chambers, uveal tract and ocular coats (anterior/intermediate uveitis/sclerouveitis, AU). Infections cause ~50% cases of AU and PU but infection may also underlie the pathogenesis of immune-mediated "non-infectious" uveitis. Dysbiosis accompanies the commonest form, HLA-B27-associated AU, while latent infections underlie BRB breakdown in PU. This review considers the pathogenesis of uveitis in the context of IP, infection, environment, and the microbiome.

The Diversity of Nutritional Metabolites: Origin, Dissection, and Application in Crop Breeding.

The chemical diversity of plants is very high, and plant-based foods provide almost all the nutrients necessary for human health, either directly or indirectly. With advancements in plant metabolomics studies, the concept of nutritional metabolites has been expanded and updated. Because the concentration of many nutrients is usually low in plant-based foods, especially those from crops, metabolome-assisted breeding techniques using molecular markers associated with the synthesis of nutritional metabolites have been developed and used to improve nutritional quality of crops. Here, we review the origins of the diversity of nutrient metabolites from a genomic perspective and the role of gene duplication and divergence. In addition, we systematically review recent advances in the metabolomic and genetic basis of metabolite production in major crops. With the development of genome sequencing and metabolic detection technologies, multi-omic integrative analysis of genomes, transcriptomes, and metabolomes has greatly facilitated the deciphering of the genetic basis of metabolic pathways and the diversity of nutrient metabolites. Finally, we summarize the application of nutrient diversity in crop breeding and discuss the future development of a viable alternative to metabolome-assisted breeding techniques that can be used to improve crop nutrient quality.