Human CCR6+ Th17 cells are present in both TCM and TEM compartments, indicating that they are able to migrate to lymphoid organs and peripheral nonlymphoid tissues. Furthermore, a small subset of CCR6+ T cells expresses the skin-homing receptor CCR10 [22]. Most of these CCR6+CCR10+ cells, however,

do not produce IL-17 nor express RORγt, but produce high levels of IL-22, a Th17-related cytokine, and express the aryl hydrocarbon receptor [22, 23]. selleck compound IL-22-producing T cells, which are operationally defined as Th22 cells, have to be considered a subtype of Th17 cells, at least until data that better define their differentiation program become available. Whatever their origin might be, it is likely that Th22 cells play a role in skin homeostasis and inflammation, in view of their homing properties and their production of IL-22, a cytokine that selectively affects keratinocyte functions, as well as their antigenic specificity [24-26]. The selective expression

of CCR6 on human Th17 cells and the role of mouse Th17 cells in the induction of experimental auto-immune encephalomyelitis (EAE) [3] prompted an investigation of the role of the CCR6/CCL20 axis in the migration of encephalitogenic T cells to the CNS. It was found that, as observed in humans, CCR6 identified mouse Th17 cells and, most notably, that the CCR6 ligand CCL20 was constitutively expressed at high levels by epithelial cells Enzalutamide solubility dmso of the choroid plexus [27], a glomerular structure that is responsible for the formation of cerebrospinal fluid. Adoptive transfer experiments Phospholipase D1 using reconstituted CCR6-deficient mice demonstrated that CCR6+ Th17 cells were the first to migrate through the choroid plexus into a noninflamed CNS where they opened up the blood brain barrier, leading to the local CCR6-independent recruitment

of a second wave of effector cells that boosted and sustained inflammation. A role for CCR6 in CNS inflammation is also supported by the finding that in multiple sclerosis (MS) patients autoreactive T cells are found exclusively in the CCR6+ compartment [28]. Since CCR6 is expressed also on a subset of human Th1 cells as well as in B cells and Treg cells, it is also possible that these subsets may migrate into the CNS through the choroid plexus and regulate inflammation. Initial studies to define the requirements for human Th17-cell differentiation were performed using naïve T cells isolated from adult peripheral blood or cord blood stimulated with anti-CD3 antibodies in the presence of exogenous recombinant cytokines.