Translational Mini-Review Series on Th17 Cells: Induction of interleukin-17 production by regulatory T cells

Abstract

Summary Uncommitted (naive) CD4+ T helper cells (Thp) can be induced to differentiate to specific lineages according to the local cytokine milieu, towards T helper type 1 (Th1), Th2, Th17 and regulatory T cell (Treg) phenotypes in a mutually exclusive manner. Each phenotype is characterized by unique signalling pathways and expression of specific transcription factors, notably T-bet for Th1, GATA-3 for Th2, forkhead box P3 ( Unexpectedly, however, a number of groups have now described conversion of Tregs to the Th17 phenotype induced by appropriate inflammatory stimuli. These observations are particularly relevant in the context of cell therapy but may also explain some of the dysregulation seen in autoimmune diseases. In this paper, we review Treg to Th17 conversion and propose some potential mechanisms for this phenomenon.

The role of Th17 and Treg responses in the pathogenesis of RSV infection

“…This plasticity is further demonstrated by the existence of Foxp3 + RORγt + CD4 + T-cells in which characteristics of both Treg cells (Foxp3 + ) and Th17 cells (RORγt + ) can be found. There seems to be considerably more plasticity in the Th17 lineage than in the Th1 and Th2 lineages which are resistant to further differentiation due to epigenetic modifications of the associated gene loci (28). At least 25% of Th17 cells once expressed Foxp3.…”

“…Human Treg cells are largely resistant to IL-6 and differentiate to the Th17 lineage in an IL-1-dependent manner. Therefore, infiltrating Treg cells at sites of infection where IL-1β is highly expressed may not necessarily exert a suppressive function, but might instead participate in the inflammatory reaction against the inciting pathogen through conversion to the Th17 lineage (28).…”

“…Their principal action is to maintain the immunological equilibrium, thus contributing to the body's homeostasis, by avoiding excessive effector T-cell activation and tissue damage during induced immune responses against infections (27)(28)(29). The Treg cells exert this function by production of the inhibitory cytokines IL-10 and transforming growth factor-β (TGF-β) (27,30,31), by interference with T-cell survival through IL-2 depletion (27,32) and by secretion of molecules that directly eliminate effector cells (27) and inhibit antigen-presenting cell maturation and functionality (27,31,33).…”

Comparison of Regulatory T Cells in Hemodialysis Patients and Healthy Controls

“…Other surface markers have also been used to delineate functional Treg subsets, such as costimulatory molecules (CD27) (15), ectoenzymes (CD39) (16), HLA-DR (17), and the memory T cell marker CD45RO (14,18). Treg phenotypes can be plastic (19), and some Treg subpopulations (especially those subpopulations in population III) (14) have the capacity to express proinflammatory cytokines and transcription factors more typically seen in Th1 and Th17 lineages (14,20,21). Consequently, successful programs of cell therapy will be critically dependent on the selection of the most appropriate Treg populations for infusion into humans.…”

MicroRNA-93 may control vascular endothelial growth factor A in circulating peripheral blood mononuclear cells in acute Kawasaki disease

“…KD may be associated with dysregulation of innate immunity and peripheral blood mononuclear cells (PBMCs)-derived vascular endothelial growth factor A (VEGF-A) may contribute to later vascular injury and remodeling in KD (2,3). Although the etiology of KD is not yet clear, current theories center on innate immunological problems (4)(5)(6)(7)(8), and several signaling pathways, including transforming growth factor-β (TGF-β), Nuclear factor of kappa B (NF-κB), and VEGF, have been reported to be involved in immune dysregulation and the pathogenesis of acute KD (2,9). VEGF-A is well known to have a role in angiogenesis, in vasodilation by indirect nitric oxide release, and in the chemotactic function of macrophages and granulocytes (10,11).…”