Monday, April 6, 2009

Th17 cells have issues with commitment

Th17 cells, so named because they secrete the protein hormone interleukin-17 (IL-17), belong to a recently-described subset of helper T cells responsible for regulating helper subsets Th1 (cellular) and Th2 (allergic).

Naïve T cells develop into different T helper subsets depending upon culture conditions. Lee and colleagues used an IL-17F reporter mouse (IL17F promoter driving expression of a surface protein Thy1.1) to test the stability of the Th17 phenotype in serial cultures. First, they caused Th17 to develop from naïve CD4+ T cells (OT-II transgene receptors specific for ovalbumin (ova) + MHC class II) by treating them in culture with TGF-beta, IL-6, anti-IFNgamma, and anti-IL-4 in the presence of IL-12p40-deficient antigen-presenting cells (APC). (Culture systems don't get much more manipulated than that!) Then, the surviving cells were phenotyped or cultured with TGNbeta or with IL-23, which stimulates the development of Th1 cells.

Several other groups had reported that Th17 cells required IL-23 for pathogenic autoimmunity. Here, Lee et al. showed that TGFbeta, but not IL-23, is essential for maintaining Th17 commitment (IL-17F expression). However, even after two cultures under Th17 conditions, IL-12 added to subsequent cultures 3 and 4 drove Th1 development and expression of interferon-gamma (IFNg, on the x-axis of figure 2, shown below).

Moreover, this final conversion by Th17 required Th1 factors STAT4 and T-bet, suggesting that Th17 might constitute a prolonged adolescence for adult Th1 cells.

Immunity 30:92-107. “Late developmental plasticity in the T helper 17 lineage”. Lee YK, Turner H, Maynard CL, Oliver JR, Chen D, Elson CO, Weaver CT.

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