Th17 cells are a subset of activated CD4+ T cells that are responsive to IL-1R1 and IL-23R signaling. They act as a bridge between adaptive and innate immunity where they promote neutrophil activation, immunity to pathogens, and inflammation. Through the study of IL-23, it was discovered that an alternate Th cell subset promotes chronic inflammation and tissue damage. Th17 cells were classified as an additional effector CD4+ T cell subset based on their independence from the transcription factors GATA3 and T-bet and the cytokines IFNγ and IL-4, used to define Th1 and Th2, respectively. While Th17 cell differentiation is driven by TGFβ and IL-6, in vitro it has been shown that IL-1β and IL-23 are also necessary in vivo for Th17 development. Th17 differentiation is driven and regulated by the lineage-defining transcription factors AHR, BATF, IκBζ, IRF4, c-Maf, RORα, RORγt, and STAT3. STAT3 is critical for Th17 differentiation and directly regulates the locus encoding IL-17 and is necessary for the expression of many transcription factors involved in Th17 differentiation. Beyond that, IL-23 is required for Th17 expansion and stabilization. Cytokines such as IFNγ, IL-27 and IL-4 are known to inhibit Th17 differentiation.

Relevant recombinant proteins

  • TGF-beta
    • Essential factor needed for Th0 to Th17 development in concert with IL-6 and IL-23
  • IL-1 beta
    • Involved in early Th17 differentiation
    • Upregulates RORγt and IRF4
    • Helps maintain Th17 cytokine profile post-polarization
  • IL-6
    • Essential in the activation of IL-17 specific transcription factor RORγt and IL-21 expression that then activates the expression of IL-17A, IL-17F, and IL-23R on TH17 cells
  • IL-21
    • Expression and autocrine feedback through STAT3, IRF4 and RORγt lead to upregulation of the IL-23R, thereby preparing Th17 cells for maturation and maintenance by the inflammatory cytokine IL-23
  • IL-23
    • Decreases the ability of de-differentiation and plasticity in Th17 cells
    • Induces expression of the characteristic Th17 cytokines
    • Essential for the survival and expansion
Relevant neutralizing antibodies

Anti-IFN-gamma, anti-IL-2, anti-IL-4, and anti-IL-27

  • Prevents the inhibition of Th17 differentiation and promotion of Th1 and Th2 cells (anti-IL-27 is not required with purified naïve T-cell culture)