Tr1 cells, but not FOXP3-positive Treg cells, isolated from healthy individuals and patients with Crohn's disease or ulcerative colitis secreted IL22, which promoted barrier function of human intestinal epithelial cells.
The interleukin (IL)-20 subfamily of cytokines consists of IL-19, IL-20, IL-22, IL-24, and IL-26, and the expression of IL-20, IL-22, and IL-24 is reported to be higher in the colon of patients with ulcerative colitis.
IL-22 plays an important role in tissue repair and inflammatory responses, and is implicated in the pathogenesis of psoriasis, ulcerative colitis, as well as liver and pancreas damage.
The possibility of MI-2 treatment in DSS-induced colitis, associated with restoration of healthy microbially diverse populations in addition to reshaping host immune modulating capacity by reducing inflammatory cytokines (tumor necrosis factor alpha, interleukin-1β [IL-1β], IL-17α, and IL-22), may be considered therapeutic for ulcerative colitis.
Here, we found that mucosal expression of genes involved in the purine metabolic pathway is altered in patients with active ulcerative colitis (UC), which is associated with elevated gene expression signatures of the group 3 innate lymphoid cell (ILC3)-interleukin (IL)-22 pathway.
Indeed, indigo naturalis, which can activate IL-22 pathway through Ahr, has been shown in a clinical trial to exhibit a strong therapeutic effect on ulcerative colitis.
This formulation also yielded a much better therapeutic efficacy against UC in a mouse model compared to hydrogel loaded with Gal-siTNF-NPs or IL-22 alone.
Because reduced IL-22 production in the gut mucosa is an established factor of HIV and DSS-induced immunopathogenesis, our data suggest that the anti-inflammatory properties of ABX464 warrant exploration in both HIV and inflammatory ulcerative colitis (UC) disease.
According to the results, we hypothesize that the elevated level of IL-2+ and IL-21+ T cells and a positive correlation between IL-21+ cells with CAI in UC patients may contribute to the pathogenesis of disease.
Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel diseases (IBDs), are characterized by high levels of IL-22 production.
Patients with UC in remission showed significantly more IL-22-positive immune cells, but no difference of epithelial c-Myc levels, in mucosa compared with healthy controls.
We showed activation of colonic IL-17/IL-22 axis and upregulation of FOXP3 to occur both in pediatric CD and in UC, indicating shared immunological characteristics.
Tumor necrosis factor alpha (TNF-α), IL-6, and IL-22, serum levels of which were elevated in patients with active UC, could induce LRG expression in COLO205 cells.
These observations indicate that IL-21 amplifies an inflammatory milieu that promotes CAC, and suggest that IL-21 blockade may be useful in reducing the risk of UC-associated colon cancer.
Expression of IL-22, IL-22R1, and DMBT1 in UC tissues was analyzed by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry.
The expression of IL-22 was enhanced in infiltrating inflammatory cells, and that of IL-22R1 and REG Ialpha was concurrently enhanced in the inflamed epithelium in UC mucosa.
Using this approach, we demonstrated a therapeutic potency for IL-22-mediated activation of the innate immune pathway in a mouse model of Th2-mediated colitis that induces disease with characteristics similar to that of IBD ulcerative colitis (UC).