IL-17-producing human peripheral regulatory T cells retain suppressive function.

Area of Science:

• Immunology
• Cell Biology

Background:

• Regulatory T cells (Tregs) and Th17 cells are crucial in autoimmune disease pathogenesis.
• Tregs are known for immune suppression, but recent findings suggest they can produce IL-17.

Purpose of the Study:

• To investigate the capacity of human Tregs to produce IL-17.
• To determine if IL-17-producing Tregs retain their suppressive function.
• To explore the plasticity of Tregs in response to inflammatory stimuli.

Main Methods:

• Isolation and cloning of human Tregs from a specific population (CD4(+)CD45RA(-)CD25(high)CCR6(+)HLA-DR(-)FoxP3(+)).
• Activation of Treg clones with pro-inflammatory cytokines (IL-1beta, IL-6) or TGFbeta.
• Assessment of IL-17 production and in vitro immune suppressive function of Treg clones.

Main Results:

• Human Tregs (CD4(+)CD45RA(-)CD25(high)CCR6(+)HLA-DR(-)FoxP3(+)) produce IL-17 when activated by IL-1beta and IL-6; TGFbeta inhibits this.
• Isolated IL-17-producing Treg clones (IL-17(+)/FoxP3(+)) maintain suppressive capacity but show plasticity.
• IL-17 production by Tregs is associated with sustained FoxP3 expression and a reversible loss of suppressive activity.

Conclusions:

• A subset of human Tregs can secrete IL-17 under inflammatory conditions.
• Inflammation can induce Tregs to produce IL-17, potentially reducing their suppressive function and exacerbating inflammation.
• This highlights a novel mechanism linking Treg plasticity to autoimmune pathogenesis.