T-regulatory/T-helper 17: promiscuous signals and fear of commitment

The insight gained recently on the differentiation of naive CD4 T cells challenges the dogma that expression of canonical transcription factors and production of signature cytokines portray a commitment to a specific lineage and a point of no return. For almost two decades now, the belief has been that naive CD4 T cells, under the guidance of environmental signals, follow a one-way road to evolve as Th1, Th2, Th17 or regulatory T cells (Tregs). The current paper, however, demonstrates a crosstalk between signals and identifies transitory T-cell states whereby a differentiating CD4(+) T cell will express a mixed Th17 and Treg phenotype. Moreover, they were able to successfully reprogram terminally differentiated Tregs into Th17 cells, suggesting that redifferentiation could occur and provides an environmental plasticity to readjust immunity. This suggests that T-cell differentiation does not necessarily follow a one-way road, but that traffic may flow in both directions.