Th17 differentiation pathway in CD4+ T cells (Th17 pathway)

The Th17 differentiation pathway in CD4+ T cells is a specialized immune program that leads to the development of T helper 17 (Th17) cells, which are defined by their production of the pro-inflammatory cytokine IL-17. This process is initiated by the integration of signals from cytokines such as IL-6, TGF-β, and IL-21, which activate the JAK-STAT signaling pathway, specifically STAT3, to induce the expression of the master transcription factor RORγt. IL-23 subsequently plays a crucial role in the stabilization and expansion of the Th17 phenotype, promoting the production of effector cytokines like IL-17A, IL-17F, and IL-22. While Th17 cells are essential for host defense against extracellular bacteria and fungi, their overactivation is a primary driver of chronic inflammatory and autoimmune diseases, including psoriasis, rheumatoid arthritis, and multiple sclerosis. Consequently, the Th17 pathway has become a major therapeutic target, with numerous approved biologics that neutralize IL-17 or IL-23, as well as small molecules targeting RORγt and JAK kinases. These therapies are highly effective but are associated with specific safety concerns, such as an increased risk of fungal infections like candidiasis.

Other names

IL-23/Th17 axisTh17 pathwayT helper 17 differentiation programIL-17/Th17 pathway

Inhibition of Th17-polarizing cytokines (IL-6, IL-23), blockade of IL-17 receptors, neutralization of effector cytokines (IL-17A, IL-17F), or inhibition of the master transcription factor RORγt.