Th17 cells

Th17 cells are induced from naive CD4+ T helper cells via cytokine signaling involving TGF-β plus IL-6 (initial differentiation) and IL-23 (maintenance/stabilization), with STAT3 and RORγt serving as master transcription factors. Once differentiated, Th17 cells secrete IL-17A, IL-17F, IL-21, and IL-22, which recruit neutrophils, induce antimicrobial peptide production by epithelial cells, and enhance barrier defense at mucosal surfaces (gut, skin, lungs)—making them critical for defense against extracellular bacteria (e.g., Klebsiella, Staphylococcus) and fungi (e.g., Candida albicans). Clinically, deficiencies in Th17 pathways (e.g., autosomal dominant hyper-IgE syndrome/Job syndrome due to STAT3 mutations) result in recurrent Staphylococcus aureus and Candida infections, cold abscesses, eczema, and connective tissue/skeletal abnormalities. Conversely, dysregulated or excessive Th17 activity is strongly implicated in autoimmune and chronic inflammatory diseases, including psoriasis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease (particularly Crohn disease), and multiple sclerosis. This has led to therapeutic targeting of the Th17 pathway—IL-17 inhibitors (secukinumab, ixekizumab) and IL-23 inhibitors (ustekinumab targets p40 subunit shared with IL-12; guselkumab targets p19 subunit specific to IL-23) are used to treat psoriasis, psoriatic arthritis, and ankylosing spondylitis. Th17 cells are part of the broader CD4+ T helper cell paradigm alongside Th1 (IFN-γ, intracellular pathogens, macrophage activation), Th2 (IL-4/5/13, helminths, allergy), and regulatory T cells (Tregs, immune tolerance)—notably, Th17 and Treg differentiation share the TGF-β signal but diverge based on the presence of IL-6.