| Regulatory T cells (Tregs) are specialized population of T cells that are engaged in |
| sustaining immunological self-tolerance and homeostasis. Deregulation of Tregs leads to |
| severe autoimmune diseases, inflammatory bowel disease, and allergy. The interleukin (IL)- |
| 6 in combination with transforming growth factor (TGF)-β drives differentiation of Th17 |
| cells by the specific transcription factor RORγt. These cells do not produce IL-4 or interferon |
| (IFN)-γ. In fact, IL-4 or IFN-γ inhibits differentiation of Th17 cells. Interestingly, TGF-β |
| alone induces differentiation of Tregs by their lineage-specific transcription factor Foxp3, |
| while IL-6 alone has inhibitory effect on Tregs and is incapable of directing differentiation of |
| Th17 cells. Hence, differentiation and function of Tregs and Th17 subsets are reciprocally |
| controlled, and their balance is critical for immune homeostasis and protection against |
| inflammatory diseases. These subsets of CD4 lineage function through their secreted |
| cytokines, while Th17 cells are defined by production of the proinflammatory cytokines IL- |
| 17 and IL-22 that mediate exacerbation of inflammation and autoimmunity, and Tregs produce |
| TGF-β and IL-10 that oppose function of Th17 cells. The Tregs may also suppress the |
| inflammatory response by CTLA-4 that inhibits B7 on the antigen-presenting cells (APCs) |
| and by secretion of granzymes and perforins that kill different effector T cells. Therefore, |
| in several autoimmune disorders, that is, experimental autoimmune encephalomyelitis (EAE), |
| experimental autoimmune uveoretinitis (EAU), and ulcerative colitis (UC), the decreased |
| frequency of Tregs and the increased frequency of Th17 cells are associated with disease severity. |
