T helper 17-related pathways (Th17 pathway)

The T helper 17 (Th17)-related pathways constitute a major pro-inflammatory axis in the adaptive immune system, primarily characterized by the differentiation and effector functions of Th17 cells. These cells are a distinct subset of CD4+ T helper cells that produce signature cytokines, including interleukin-17A (IL-17A), IL-17F, IL-21, and IL-22, under the control of the master transcription factor RORγt [1, 5, 16]. The pathway is initiated by cytokines such as IL-6, TGF-beta, and IL-1beta, and is further stabilized and expanded by IL-23 [4, 16, 18]. While essential for host defense against extracellular bacteria and fungi, particularly at mucosal barriers, overactivation of the Th17 axis is a central driver of various autoimmune and chronic inflammatory diseases such as psoriasis, ankylosing spondylitis, and rheumatoid arthritis [1, 3, 6]. Therapeutic strategies targeting this pathway have proven highly effective and include monoclonal antibodies that neutralize IL-17 or IL-23, as well as inhibitors of the IL-17 receptor [2, 4, 7]. However, modulation of these pathways carries risks, such as increased susceptibility to fungal infections and potential exacerbation of inflammatory bowel disease in certain contexts [1, 10, 18].

Other names

IL-23/Th17 axisIL-17/Th17 pathwayTh17 signaling pathwayT helper 17 cell pathwayIL-17 pathway

Inhibition of Th17 cell differentiation, neutralization of Th17-derived cytokines (IL-17A, IL-17F, IL-22), blockade of cytokine receptors (IL-17RA, IL-23R), or inhibition of master transcription factors (RORγt).