This is an introductuion from a research paper: ' Interleukin 17 (IL-17)–producing T helper cells (TH-17 cells) are now accepted as the main population of pathogenic T cells driving autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE)1,2 and collagen-induced arthritis3, the mouse models for multiple sclerosis and rheumatoid arthritis, respectively. TH-17 cells are characterized by their STAT3-dependent expression of the transcription factor RORgt4 and production of the hallmark cytokines IL-17 and IL-22 (ref. 5). Initial work to identify the factors involved in the differentiation of the TH-17 cell lineage has provided two observations. First, IL-23 drives the production of IL-17 by memory T cells6. Second, in mice with a genetic deficiency of IL-23, resistance to EAE correlates with the lack of IL-17-producing T cells in the central nervous system (CNS)1. Subsequent studies showed that TGF-b, when combined with proinflammatory cytokines such as IL-6, is the strongest inducer of RORgtproteinandTH-17 cells in mice2,7,8. In contrast, transforming growth factor-b (TGF-b) alone drives expression of the lineage-specific transcription factor Foxp3, leading to a regulatory T cell (Treg cell) phenotype2. In vitro, IL-23 seems to be not involved in the early differentiation of TH-17 cells, most probably because of the small amounts of the receptor for IL-23 (IL-23R) on naive T cells. Ligation of the T cell antigen receptor (TCR) in the presence of IL-6 has been shown to upregulate IL-23R4,althoughIL-6 may not be the only factor able to do this.
 Consistent with the idea that this population is a distinct helper cell lineage, the differentiation of TH-17 cells is inhibited by the T helper type 1 (TH1) and TH2 hallmark cytokines interferon-g (IFN-g)and IL-4, respectively9. IL-27 and IL-25, originally defined for their TH1- and TH2-promoting activities, also regulate TH-17 cells10–12, although this does not seem to occur through the induction of IFN-g or IL-4. In a further twist, TH-17 cells have again been shown to have intimate links with Foxp3-expressing Treg cells, with both IL-2 (through STAT5) and retinoic acid (binding to RORgt) acting to negatively regulate RORgt while promoting Foxp3 (refs. 13,14). It seems that most of these factors regulate the early differentiation of TH-17 cells. Thus, despite being induced by the ‘anti-inflammatory’ TGF-b, the TH-17 population is rigorously regulated by many pathways.
 There is an unresolved contradiction in the data on TGF-b and inflammatory diseases such as EAE. Studies have shown convincingly that TGF-b is required for TH-17 differentiation in vitro and in vivo. Experiments have shown that TGF-b signaling is required by CD4+ T cells for the induction of pathogenic TH-17 cells in vivo and furthermore that blocking TGF-b locally at the time of immunization abrogates EAE induction15. It has also been reported that, unexpectedly, expression of TGF-b under control of the Il2 promoter in a myelin oligodendrocyte glycoprotein (MOG)–specific T cell transgenic mouse leads to exacerbated EAE because of greater numbers of TH-17 cells2. However, there is a substantial body of evidence showing that TGF-b has anti-inflammatory effects in the same disease settings. TGF-b has been noted to increase during the remission phase of EAE16, and TGF-b-producing T cells can mediate oral tolerance in this disease17,18. Amelioration of EAE and collagen-induced arthritis has also been achieved by administration of soluble TGF-b1 (refs. 19,20); conversely, systemic administration of antibodies blocking TGF-b in vivo leads to exacerbation of EAE15. These studies were mostly done before TH-17 cells ‘appeared on the scene’; hence, they assumed effects on TH1 cells and now deserve reconsideration.                                                                                                                                                                                                       The data (in mice at least) irrefutably define TGF-b as a chief factor in the induction of pathogenic TH-17 cells in vivo. However, the issue remains of whether TGF-b continues to promote the pathogenic function of TH-17 cells after initial activation or whether TH-17 cells instead become sensitive to the immunoregulatory effects of TGF-b at a specific time. To address that, we compared the response of activated myelin-reactive T cells from immunized mice to culture with IL-23 or with TGF-b plus IL-6 in terms of phenotype, production of IL-17, gene expression and pathogenic activity after transfer into naive hosts. We found that whereas stimulation with TGF-b and IL-6 continuously promoted IL-17 production in activated T cells, it abrogated the pathogenic function of TH-17 cells in vivo. In addition, IL-10 production was enhanced by the stimulation of activated TH-17 cells with TGF-b and IL-6, thereby ‘directing’ these cells to a more regulatory function.' Summarise this in bullet points