T-helper 17 immune response (Th17 response)

The T-helper 17 (Th17) immune response is a specialized branch of the adaptive immune system characterized by the production of signature cytokines such as interleukin-17 (IL-17A, IL-17F), IL-22, and IL-21 [6, 10, 12]. This response is primarily driven by the differentiation of CD4+ T cells under the influence of cytokines like IL-6, TGF-beta, and IL-23, with the transcription factor ROR gamma t serving as the master regulator [10, 13, 17]. While essential for host defense against mucosal fungal (e.g., Candida) and bacterial pathogens (e.g., Staphylococcus), dysregulation of the Th17 pathway is a central driver in various autoimmune and chronic inflammatory diseases [1, 12, 16]. Therapeutic strategies targeting this response focus on neutralizing key effector cytokines or blocking their receptors to alleviate systemic and local tissue inflammation [3, 4, 8]. Monoclonal antibodies like Secukinumab and Ixekizumab target IL-17A, while others like Guselkumab target the IL-23 driver to prevent Th17 maintenance [3, 9]. These therapies have significantly improved outcomes for patients with psoriasis, ankylosing spondylitis, and psoriatic arthritis [3, 11]. However, because this pathway is critical for mucosal immunity, its inhibition is associated with an increased risk of fungal infections and potential exacerbations of inflammatory bowel disease [1, 8, 9].

Other names

Th17 pathwayTh17 cell-mediated immunityInterleukin-17-mediated immune responseIL-17/IL-23 signaling axis

Neutralization of pro-inflammatory cytokines (IL-17A, IL-17F, or IL-23 p19/p40 subunits) or competitive blockade of cytokine receptors (IL-17RA) to inhibit downstream inflammatory signaling cascades and reduce neutrophil-mediated tissue damage.