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.
Box 1: T helper 17 and regulatory T cells.