How T cells take developmental decisions by using the aryl hydrocarbon receptor to sense the environment

摘要

For the last 25 y or so, T helper (Th)-cell responses have been classified according to either Th1 or Th2 depending on whether these T cells produce IFN-γ or IL-4. While Thl cells produce IFN-γ and induce mac-rophage-driven inflammation, Th2 cells secrete IL-4 and drive eosinophilic inflammation. Following the discovery of Th17 cells whose signature cytokine is IL-17A, a vigorous debate on the classification of Th-cell lineages has been unleashed. In addition to IL-17, Th17 cells secrete IL-17F, IL-21, and IL-22. The main argument for Thl7 cells to be distinct from Thl and Th2 cells was that they could be generated in the absence of Th1-associated (T-bet, STAT1, and STAT4) and Th2-associated (STAT6) transcription factors, respectively (reviewed in 1). However, the fact that Th17 cells appear unstable in vivo and the unresolved issues on the role of IL-23 for either their differentiation or stabilization, as well as the discovery of even more "T-cell lineages" like Th9 and Th22, have again spurred the debate on the plasticity of Th cells. The classification into Th1, Th2, and Th17 is still and foremost based on the distinct profile of cytokines that are produced by these T-cell subsets. In an effort to characterize other genes that would be differentially expressed in Th-cell subsets, the aryl hydrocarbon receptor (Ahr) gene was recognized to be silent in Thl and Th2 cells but highly transcribed in Th17 cells (2, 3). In a study published in PNAS, Quintana et al. (4) investigate the functional relevance of AHR expression by specific Th-cell subsets in a disease model of CNS autoimmunity.