Emerging topics and new perspectives on regulatory and effector T cells.

It is well accepted that the balance of immunity between effector and regulatory T cells determines the outcome of autoimmune and chronic inflamma-tory diseases. Concerning the topic of 'Regulatory and Effector T Cells' as published in this issue of Journal of Molecular Cell Biology, several investigators have provided important new information. T-helper 1 (Th1) and Th2 cells represent the classical type of Th or effector cells. However, recent studies have also identified several new cell subsets of Th cells, including IL-9-producing T (Th9), IL-17-producing T (Th17), IL-22-producing T (Th22), and T follicular helper (Tfh) cells, extending the Th cell structure. Given their crucial role in the pathogenesis of autoimmune and inflammatory diseases , Th17 cells have received much attention.cantly more potent in initiating signaling and causing autoimmune responses than other cytokines produced by these cells. The differentiation of mouse Th17 cells needs the combination of IL-6 and transforming growth factor-beta (TGF-b) (Bettelli et al., 2006), although IL-6-or TGF-b-independent pathways may also contribute to Th17 cell differentiation. The role of TGF-b in human Th17 cell differentiation is still controversial. Of note, the IL-21 and IL-1 signal pathways seem to be important in initiating Th17 cell development. IL-21 and IL-23 are also known to sustain and expand Th17 cells. Dr Ryffel's group provides an updated account of the differentiation and function of Th17 cells, particularly during lung injury and inflammatory disease. They demonstrated that lung injury or aller-gen exposure leads to NLPR3 activation, with formation of the NLPR3 inflammasome complex and caspase-1 activation resulting in mature IL-1b, which may elicit IL-17 production. Traditionally, asthma is elicited by Th2 cells. It is still unclear whether Th17 cells work independent or together with Th2 cells in the development of asthma. They suggest that Th17 cells promote asthma through modulation of Th2 cells. In fact, IL-17E or IL-25, another IL-17 member, can induce Th2 cytokines and promote allergy. It is also possible that IL-17 regulates allergic responses independent of Th2 cells but Th2 cells promote asthma through Th17 cells since IL-4 does regulate IL-17 levels. It has been widely accepted that Tregs are critically involved in immune tolerance and homeostasis. Although this concept was suggested in early 1970s, it was resuscitated in 1990s when thymus-derived CD4 + CD25 + cells were identified as natural Tregs (nTregs) (Sakaguchi et al., 1995). While Foxp3 has been identified as a unique marker and functional transcription factor for these …