A role for the IL-23/IL-17 pathway in the pathogenesis of chronic intestinal inflammation in inflammatory bowel disease has emerged from both animal and human studies.
Interleukin-17 (IL-17) has been proved to be involved in the pathogenesis of several autoimmune diseases, including lupus, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease.
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.
Our data thus indicated that the HMGB1-TLR2/4-DCs-IL-23 cascade pathway enhances the functions of ILC3s to produce IL-17 and IL-22, and this signal way might play a vital role in the development of IBD.
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.
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.
Areas covered: A literature search to March 2016 was performed to identify the most relevant reports on the role of the IL-23/IL-17 axis in IBD and on the different molecules targeting this pathway.
We did not find any correlation between serum concentrations of TL1A and IL-17A or changes of CD4(+) or CD8(+) lymphocytes phenotype in patients with IBD.
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).
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.
All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17(+) T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease.
We report the development of safe lactic acid bacterium Lb. salivarius with the ability to simultaneously bind IL-17A, IL-23 and TNFα that could be administered orally for the treatment of 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.