Intestinal Th2 and Th17 programs (Th2/Th17)

The Intestinal Th2 and Th17 programs refer to the complex immunological pathways and transcriptional networks that regulate the differentiation and activity of Type 2 and Type 17 helper T cells within the gut mucosa. These programs are not a single molecular target but rather a collection of signaling events driven by master transcription factors like GATA3 (for Th2) and RORγt (for Th17). In a healthy intestine, these programs maintain homeostasis by defending against parasites and fungi while supporting epithelial barrier integrity (Omenetti & Pizarro, 2015). However, their dysregulation is a hallmark of inflammatory bowel diseases (IBD), where Th17 cells can acquire Th2-like characteristics, leading to chronic, non-resolving inflammation (Wang et al., 2017). Therapeutic intervention typically involves targeting specific components of these programs, such as the cytokines IL-17, IL-23, or IL-4/13, rather than the entire program itself. Drugs like ustekinumab and risankizumab are used to modulate the Th17/IL-23 axis in Crohn's disease, while agents targeting Th2 cytokines are explored for ulcerative colitis (Nielsen et al., 2023). A significant challenge in targeting these programs is their inherent plasticity and the risk of disrupting protective mucosal immunity, which can lead to opportunistic infections or paradoxical disease worsening.

Other names

Th2/Th17 axisIntestinal Type 2 and Type 17 immune responsesTh2 and Th17 signaling pathways

Inhibition of specific cytokines (IL-17, IL-23, IL-4, IL-13) or transcription factors (RORγt) that mediate the Th2 and Th17 immune responses.