Retinoic Acid Related Orphan Nuclear Receptor gamma T (RORγT) is a lineage specifying transcription factor for IL-17 expressing cells, which may contribute to the pathogenesis of Inflammatory Bowel Disease (IBD).
Experimental evidence "proves" that IL-17 plays a critical role in the pathogenesis of inflammatory bowel disease, but blocking IL-17 makes Crohn's disease worse.
After 1 year of follow-up, the odds of having IBD were 2.85 (<i>p</i> = .0213) and 1.42 (<i>p</i> = .1891) times higher in the anti-IL-17a and PDE4i cohorts, respectively, compared to the biologic-naïve cohort, and 2.86 (<i>p</i> = .0253) and 1.21 (<i>p</i> = .4978) times higher compared to the non-IBD-indicated biologic cohort.
TAK-828F strongly inhibited IL-17 gene expression with IC<sub>50</sub> values from 21.4 to 34.4 nmol/L in PBMCs from anti-TNF mAb naive and treatment-failure patients of IBD.
IL-17-producing Th17 cells and IFN-γ and IL-17 double-producing Th1/17 cells have been identified as the pathogenic cells in inflammatory bowel disease (IBD).
Serious adverse effects occur less frequently and specific to the psoriasis treatment option, such as inflammatory bowel disease and candida infections with IL-17 inhibitors, tuberculosis with certolizumab pegol, and psychiatric events with apremilast.
Up to December 2018, eight cases of new-onset inflammatory bowel disease (IBD) were reported in the literature in patients being treated with secukinumab, an interleukin-17A antagonist prescribed for dermatologic or rheumatologic indications.
Importantly, intestinal NIK signaling is active in mouse models of colitis and patients with inflammatory bowel diseases; meanwhile, constitutive NIK signaling increases the susceptibility to inflammatory injury by inducing ectopic M-cell differentiation and a chronic increase of IL-17A.
Contrastingly, enterotoxigenic Bacteroides fragilis (ETBF) is highly associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC), rapidly inducing IL-17-dependent murine colitis and tumorigenesis.
However, it is lack of depth in whether TGP regulate T helper 17 cell (Th17) / T regulatory cell (Treg) immune balance or interleukin 23 (IL-23) / IL-17 axis to achieve the goal of treating IBD.
Spondyloarthritis (SpA), a chronic inflammatory, rheumatic disease, and hidradenitis suppurativa (HS), a chronic, debilitating, inflammatory skin disease, share several clinical and pathophysiological features, such as the association with inflammatory bowel disease and elevated cytokine levels IL-17 and TNF-α.
Compared with non-inflamed tissues, both total mast cells and IL-17A-positive mast cells were increased in psoriatic skin dermis and in submucosa from inflammatory bowel disease gut.
This is the first case report of de-novo severe Crohn's-like IBD in association with the use of Ixekizumab requiring rescue with escalated dosing of anti-TNF therapy and highlights the importance of close monitoring in patients being treated with IL-17 inhibitors, especially in those patients with known risk factors for inflammatory bowel disease.
ILC3 contribute to the progression and aggravation of IBD while both IL-22 and IL-17, along with IFN-γ, are overexpressed by the dysregulation of NCR<sup>-</sup> ILC3 or NCR<sup>+</sup> ILC3 function and the bias of NCR<sup>+</sup> ILC3 towards ILC1 as well as regulatory ILC dysfunction in the pathological state.
Notably, however, IL-17 blockade remains ineffective or even pathogenic against important autoimmune diseases such as inflammatory bowel disease (IBD).
The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.
IL-23-mediated Th-17 cell activation and stimulation of IL-17-driven pro-inflammatory axis has been associated with autoimmunity disorders such as Inflammatory Bowel Disease (IBD) or Crohn’s Disease (CD).