An autonomous activation of interleukin-17 receptor signaling sustains inflammation and promotes disease progression

Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients

“…Our novel approach designed with the intention of downregulating the Th1 inflammatory response, followed by IL-17A blockade and was based on several experimental studies evaluating anti-IL-17 therapy, in which worsening of colitis in patients 21 or glomerulonephritis in animal models 34 was observed in the presence of an active Th1 pro-inflammatory response. More recently, a study described that autonomous activation of IL-17 receptor is responsible for continuous inflammation 35 . This could explain the lack of efficacy in some IL-17-associated pathologies when IL-17A inhibition is administered alone.…”

IL-17 in wound repair: bridging acute and chronic responses

“…It is crucial to note that TRAF6 helps activate the MAPK pathway that IL-17 induces to activate transcription factors like AP-1 [ 57 ]. Act1 mediates this activation [ 58 ]. There are a number of regulatory mechanisms that are used to fine-tune the TRAF6-mediated IL-17 signal transduction in order to reduce the inflammation that is generated by IL-17 [ 59 ].…”

Interplay of IL‐17A/IL‐17RA signaling with microbial homeostasis in systemic anti‐tumoral responses

“…IL‐17A, a pivotal pro‐inflammatory cytokine primarily derived from T‐helper 17 (Th17) cells, was initially recognized for its essential role for its fundamental contribution to the host's defense mechanism against various microbes, notably extracellular fungi and bacteria. 2 , 3 , 4 IL‐17RA is widely expressed across cell types, facilitating the potential reactivity of numerous cells to this cytokine, particularly emphasizing the analysis of non‐immune cell types, such as mesenchymal cells and epithelial located within tissues experiencing inflammation or disease. In terms of functionality, IL‐17A plays a contributory role in the pathogenesis of autoimmune disorders, encompassing conditions such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and psoriasis.…”

“…In terms of functionality, IL‐17A plays a contributory role in the pathogenesis of autoimmune disorders, encompassing conditions such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and psoriasis. 1 , 2 , 5 Apart from its involvement in autoimmune disorders, IL‐17A emerges as a key player in cancer, with notable implications in pancreatic ductal adenocarcinoma (PDAC), where IL‐17A/IL‐17RA signaling profoundly impacts various facets of tumor biology including cell proliferation, growth, progression, microenvironmental remodeling, and resistance to treatment, all mediated by the inflammatory milieu within the tumor microenvironment. 1 , 4 , 5 Studies reveal context‐dependent effects of IL‐17A in cancer, demonstrating instances of Th17‐mediated anti‐tumor immunity and IL‐17A‐producing cells contributing to CD8 + T cell exhaustion in melanoma, ultimately enhancing the efficacy of immunotherapeutic approaches.…”