Th17

Th17 cells differentiate from naive CD4+ T cells under the influence of TGF-β, IL-6, and IL-23, with the master transcription factor RORγt driving their lineage commitment. They secrete IL-17A, IL-17F, IL-21, and IL-22, which recruit neutrophils, induce antimicrobial peptide production by epithelial cells, and enhance barrier defense against extracellular bacteria (e.g., Klebsiella, Staphylococcus) and fungi (e.g., Candida albicans). Patients with deficiencies in Th17 differentiation pathways (e.g., Job syndrome/hyper-IgE syndrome due to STAT3 mutations) suffer from recurrent staphylococcal skin infections, mucocutaneous candidiasis, and characteristic coarse facies, retained primary teeth, and eczema. Conversely, dysregulated or excessive Th17 activity contributes to autoimmune and inflammatory diseases such as psoriasis, psoriatic arthritis, ankylosing spondylitis, multiple sclerosis, and inflammatory bowel disease (particularly Crohn disease). This has led to the development of biologic therapies targeting the Th17 pathway, including IL-17 inhibitors (secukinumab, ixekizumab) and IL-12/23 inhibitors (ustekinumab), used clinically for psoriasis, psoriatic arthritis, and ankylosing spondylitis. Th17 cells are functionally distinct from Th1 (IFN-γ, intracellular pathogens) and Th2 (IL-4, IL-5, IL-13, helminths/allergy) subsets, though plasticity between subsets can occur. Understanding the Th17 axis is high-yield for both immunology and pharmacology sections of USMLE Step 1, as well as for correlating clinical presentations of autoimmune disease with targeted biologic therapies on Step 2.