Figure 3.

Genetic and environmental factors influencing immune cell entry into the brain. Encounter of microbes takes place at the inner and outer surfaces of the body equipped with special barrier forming epithelia and innate immune cells residing behind these barriers. Priming of T cells in skin and gut-draining lymph nodes imprints their effector function, i.e. expression of trafficking molecules. Pale-skinned people have a higher risk of developing MS as compared to people with black skin. The schematic representation shows imprinting of trafficking properties in T-cells primed in the skin and the gut (adapted from (2), chapter 14). Experimental animal studies have shown that autoagressive T cells primed in skin-draining lymph nodes express CXCR6 and can enter the CNS white and grey matter, while when these T cells are primed in gut-draining lymph odes they express P2rx7 and only infiltrate CNS white matter. How skin color and the gut microbiome of the African population affects T cell priming and their CNS homing properties remains to be shown. The shapes of the cell types were adapted from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Common Attribution 3.0 Generic License.