The transient nature of the Th17 phenotype


  • Note added in proofs: After this commentary was accepted for publication, Ghoreschi et al. reported that even murine Th17 cells do not require TGF-b signalling for their differentiation, which occurs in response to the combined activity of IL-1b and IL-23, whereas TGF-b may play only an indirect role by suppressing T-bet expression and the development of Th1 cells. This study demolishes the still ruling dogma on the origin of Th17 cells and fully supports all our findings [14, 17, 19, 27, and this Commentary], as well as our concept that studies in humans have better depicted Th17 cells than initial studies in mice [23]. Ghoreschi, K., Laurence, A., Yang, X. P., Tato, C. M., McGeachy, M. J., Konkel, J. E., Ramos, H. L., Wei, al. Generation of pathogenic T(H)17 cells in the absence of TGF-b signalling. Nature. 2010. 467: 967-971.


CD4+ Th lymphocytes represent a heterogeneous population of cells that play an essential role in adaptive immunity. In addition to type 1 (Th1) and type 2 (Th2) cells, a third subset of CD4+ Th effector cells has recently been discovered, named type 17 (Th17) because of its unique ability to produce interleukin (IL)-17. Initial studies in mice suggested that Th17 cells are the pathogenic cells in autoimmune disorders, whereas Th1 cells are protective. Studies in humans have demonstrated the plasticity of Th17 cells and their ability to convert to Th1 cells. This Th17 to Th1 cell plasticity has also been confirmed in mice and, furthermore, it was found that Th17 cells appear to be pathogenic only when they shift to Th1 cells. A study in this issue of the European Journal of Immunology uses an IL-17 fate mapping mouse strain, which permits the identification of the cells that have been IL-17 producers, to provide definitive evidence that Th17 cells, either generated in vitro or in vivo, represent a transient phenotype that tend to convert into IFN-γ-producing cells. Our Commentary discusses this interesting point in light of previous data suggesting the same concept.