Interleukin-17 and Nucleotide-binding Oligomerization Domain-like receptor pathway components (IL-17 and NLR pathway components)

The Interleukin-17 (IL-17) and Nucleotide-binding Oligomerization Domain-like receptor (NLR) pathway components represent a complex network of signaling molecules that are central to the regulation of the host's inflammatory response. The IL-17 pathway is primarily driven by the IL-17 family of cytokines, such as IL-17A and IL-17F, which signal through a heterodimeric receptor complex (IL-17RA and IL-17RC) to activate proinflammatory genes via the adaptor protein Act1. The NLR pathway involves intracellular sensors like NOD1, NOD2, and the NLRP3 inflammasome, which detect pathogen-associated or danger-associated molecular patterns to trigger the activation of NF-κB or the maturation of interleukin-1β (IL-1β). These two pathways are highly interconnected; for example, IL-1β produced via the NLR/inflammasome pathway is a critical driver of Th17 cell differentiation and subsequent IL-17 production, creating a feed-forward loop that amplifies chronic inflammation. Dysregulation of these components is a hallmark of various autoimmune and autoinflammatory diseases, including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Therapeutic strategies targeting this axis include monoclonal antibodies that neutralize IL-17 (e.g., secukinumab) or block its receptor (e.g., brodalumab), as well as agents that inhibit NLR-derived cytokines like IL-1β (e.g., canakinumab) or the NLRP3 inflammasome itself.

Other names

IL-17 signaling pathwayNOD-like receptor signaling pathwayTh17/Inflammasome axisIL-17/NLR axis

Inhibition of proinflammatory signaling through the neutralization of IL-17 cytokines, blockade of IL-17 receptors, or suppression of the NOD-like receptor pathway and its downstream products like the NLRP3 inflammasome and interleukin-1β.