Th17 and non-classic Th1 cells in chronic inflammatory disorders: two sides of the same coin.

Th17 lymphocytes, beyond their protective role in the clearance of extracellular pathogens, also play a role in the pathogenesis of several autoimmune and inflammatory diseases, such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel diseases, psoriasis and contact dermatitis. Nevertheless, they are very rare at inflammatory sites in comparison with other T cell subsets. Recently, this rarity has been explained by the finding that Th17 cells rapidly shift into the Th1 phenotype in the presence of IL-12 and/or TNF-α as well as by the fact that they possess self-regulatory mechanisms limiting their own expansion. Th17 lymphocytes that have shifted towards a Th1 phenotype seem to be particularly aggressive and more pathogenic than the Th17 unshifted cells. As a consequence, the Th17-derived Th1 cells, named non-classic Th1 cells, can become a possible target for the therapy of some inflammatory disorders. In particular, convincing evidence has recently been accumulated indicating that this subset can play a role in Crohn's disease and juvenile idiopathic arthritis. More importantly, it has been shown that TNF-α inhibitors, which are used for the treatment of such diseases, appear to be able to inhibit the transition of Th17 lymphocytes to the non-classic Th1 phenotype, and thus they possibly help to dampen inflammation and arrest disease progression. Based on this context, the definition of the soluble factors involved in the shifting from Th17 towards non-classic Th1 subset as well as the comprehension of their respective pathogenic role in human inflammatory disorders would be of great help for developing novel therapeutic strategies.