T-helper 17 cell-mediated inflammatory pathway (Th17 pathway)

The T-helper 17 (Th17) cell-mediated inflammatory pathway is a critical component of the adaptive immune system, primarily defined by the production of the IL-17 family of cytokines (Gaffen et al., 2014, Nature Reviews Immunology). This pathway is orchestrated by the differentiation of naive CD4+ T cells into Th17 cells under the influence of cytokines like TGF-β, IL-6, and IL-1, with IL-23 being essential for their expansion and pathogenicity (McGeachy et al., 2019, Immunity). The master transcription factor RORγt regulates the expression of effector cytokines including IL-17A, IL-17F, and IL-22, which act on various target cells to induce the production of pro-inflammatory mediators and chemokines (Ivanov et al., 2006, Cell). While vital for host defense against extracellular pathogens like Candida albicans, overactivation of this axis is a hallmark of several autoimmune and chronic inflammatory disorders, most notably psoriasis and ankylosing spondylitis (Blauvelt & Chiricozzi, 2018, J Am Acad Dermatol). Pharmacological targeting of this pathway has revolutionized the treatment of these conditions through the use of monoclonal antibodies that neutralize IL-17A (e.g., secukinumab), the IL-17 receptor (e.g., brodalumab), or the p40/p19 subunits of IL-23 (e.g., ustekinumab, guselkumab) (Lebwohl et al., 2015, NEJM). However, therapeutic blockade of this pathway carries risks, including an increased susceptibility to fungal infections and potential flares of inflammatory bowel disease in certain patient populations (Hueber et al., 2012, Gut).

Other names

IL-23/IL-17 axisTh17 signaling pathwayT-helper 17 cell pathwayTh17 axis

Monoclonal antibodies target and neutralize specific cytokines (IL-17A, IL-17F, IL-23) or their receptors (IL-17RA) to inhibit the downstream inflammatory signaling cascade and reduce tissue inflammation (Blauvelt & Chiricozzi, 2018, J Am Acad Dermatol).