CD4+ T-cell differentiation pathways governing regulatory T cells and Th17 cells (Treg/Th17 axis)

The CD4+ T-cell differentiation pathways governing regulatory T (Treg) cells and Th17 cells represent a critical biological axis in the adaptive immune system that maintains the balance between pro-inflammatory responses and immune tolerance [1]. Th17 cells, characterized by the expression of the transcription factor ROR-gamma-t (RORgt) and the secretion of cytokines like IL-17, are essential for defense against extracellular pathogens but are also primary drivers of autoimmunity [2]. Conversely, Treg cells, defined by FOXP3 expression, serve to suppress immune activation and prevent self-reactivity [1]. The differentiation of these two lineages is reciprocally linked; for instance, TGF-beta is required for the induction of both FOXP3+ Tregs and, in the presence of pro-inflammatory cytokines like IL-6 or IL-21, RORgt+ Th17 cells [2, 3]. Dysregulation of this balance is a hallmark of numerous inflammatory conditions, including psoriasis, multiple sclerosis, and rheumatoid arthritis [4]. Pharmacological intervention typically targets specific components of this pathway, such as IL-17 or IL-23 receptors, to restore immune homeostasis and treat chronic inflammatory diseases [5].

Other names

Treg/Th17 balanceTh17/Treg differentiation axisCD4+ T-cell lineage commitmentReciprocal Th17/Treg differentiation pathway

Modulation of the Th17/Treg balance through the inhibition of pro-inflammatory cytokines (IL-17, IL-23) or the RORgt transcription factor, or the enhancement of Treg-mediated suppression.