Immunology Select

T helper 17 (Th17) cells are a recently discovered lineage of T lymphocytes that have been implicated in auto-immunity and inflammation. Several recent studies reveal new factors that promote or impair differentiation of T lymphocytes into Th17 cells, thereby contributing to our understanding of how this lineage is specified and how to combat Th17-mediated autoimmunity. Differentiation of naı¨ve T helper cells is initiated by dendritic cells, but the lineage fate of these helper cells is determined by different cytokines. For example, after stimulation by dendritic cells, differentiation towards the Th17 lineage—which contributes to autoimmunity—is stimulated by TGF-b and interleukin (IL)-6. In the absence of IL-6, TGF-b stimulates the differentiation of naı¨ve T lymphocytes into regulatory T cells, which suppress the immune system. Mucida et al. (2007) set out to investigate how TGF-b mediates these diverse events. The authors compared the ability of mucosal dendritic cells from the mesenteric lymph node (MLN) and peripheral dendritic cells from the spleen to stimulate differentiation of activated CD4 + T cells into Th17 cells. MLN dendritic cells did not stimulate formation of Th17 cells to the same degree as spleen dendritic cells despite the presence of TGF-b and IL-6. Given that retinoic acid (RA) produced by mucosal dendritic cells can stimulate the homing of certain types of T cells, Mucida et al. tested whether RA was impairing the ability of MLN dendritic cells to promote Th17 differentiation. The authors showed that MLN dendritic cells could promote Th17 differentiation in the presence of an antagonist for the retinoic acid receptor (RAR), LE135. Furthermore, addition of RA to spleen dendritic cells prevented their ability to stimulate differentiation of CD4 + T cells into Th17 cells. Next, Mucida et al. demonstrated that expression of RORgt (an orphan nuclear receptor that regulates Th17 differentiation) induced by TGF-b, and cytokines was reduced in the presence of RA. In addition to preventing Th17 differentiation in vivo, the authors showed that RA positively influences the differentiation of CD4 + T cells into regulatory T cells in a manner dependent on IL-2 signaling. These results suggest that vitamin A deficiency could result in increased inflammatory immune responses by favoring differentiation of Th17 cells. Given the importance of IL-6 in determining the fate of Th17 cells, Korn et al. (2007) examined the ratio of regulatory T cells (Tregs) versus Th17 cells in immunized IL-6-deficient mice. As predicted, IL-6-deficient mice had impaired production of …